Thioamide compounds, method of making and method of using thereof

ABSTRACT

The present invention relates to novel thioamide derivatives of formula (I) and formula (Ia): 
                         
wherein, R 3 , R 4 , R 5 , R 6 , R 7 , P, Q, T, V, W, X, Y, Z, a, m and n are as defined in the description, compositions thereof, processes for their preparation and their uses as pesticides.

INCORPORATION BY REFERENCE

This application claims the benefit of U.S. Provisional Application No.61/107,114, filed Oct. 21, 2008 which is incorporated herein byreference in its entirety.

Any foregoing applications and all documents cited therein or duringtheir prosecution (“application cited documents”) and all documentscited or referenced in the application cited documents, and alldocuments cited or referenced herein (“herein cited documents”), and alldocuments cited or referenced in herein cited documents, together withany manufacturer's instructions, descriptions, product specifications,and product sheets for any products mentioned herein or in any documentincorporated by reference herein, are hereby incorporated herein byreference, and may be employed in the practice of the invention.

Citation or identification of any document in this application is not anadmission that such document is available as prior art to the presentinvention.

FIELD OF THE INVENTION

The present invention relates to novel thioamide derivatives of formula(I) and (Ia):

wherein, R₃, R₄, R₅, R₆, R₇, P, Q, T, V, W, X, Y, Z, a, m and n are asdefined in the description, compositions thereof, processes for theirpreparation and their uses as pesticides.

BACKGROUND OF THE INVENTION

The control of parasites, particularly endoparasites which parasitizeanimals, by means of active material having a cyanoethylamide group hasbeen described by many patents or patent application such asInternational Patent Publications No. WO 2002/049641, WO 2003/097036, WO2003/097585, WO 2003/104187, WO 2004/000793, WO 2005/044784, WO2005/05802, WO 2005/121075 and WO 2006/043654 as well as in EP 953565(U.S. Pat. No. 6,239,077) and EP 1445251.

Novel aryl-azol-2-yl-cyanoethylamide derivatives of the formula:

are described in US 2003/0312272 A1 to Soll et al., which is herebyincorporated by reference in.

However, none of the foregoing publications describe the compounds offormula (I) or formula (Ia), the method of making or the method of usingpossess activity as pesticides, particularly for controllingendoparasitic pests in animals.

OBJECTS AND SUMMARY OF THE INVENTION

The present invention relates to novel thioamide derivatives of formula(I) and (Ia):

wherein:

-   R₁, R₂, R₈, R₉, R₁₀ and R₁₁, independently of one another, are    hydrogen, cyano, nitro, halogen, alkyl, cycloalkyl, haloalkyl,    alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl,    alkylsulfonyl, haloalkylsulfonyl, SF₅, arylthio, alkoxy,    cycloalkyloxy, haloalkoxy, alkylcarbonyl, haloalkylcarbonyl,    alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, alkylamino,    di(alkyl)amino, unsubstituted or substituted aryl, unsubstituted or    substituted heteroaryl, or unsubstituted or substituted phenoxy,    whereby the substituents may each be independent of one another and    are selected from the group consisting of cyano, nitro, halogen,    alkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy,    haloalkoxy, alkylcarbonyl, haloalkylcarbonyl, alkylsulfinyl,    haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, or SF₅;-   R₃, R₄ and R₅, independently of one another, are hydrogen, halogen,    alkyl, haloalkyl; unsubstituted or substituted cycloalkyl, wherein    the substituents may each be independent of one another and are    selected from the group consisting of halogen and alkyl;    unsubstituted or substituted aryl, whereby the substituents may each    be independent of one another and are selected from the group    consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio,    haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl,    haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl,    haloalkylsulfonyl, SF₅, alkylamino, di(alkyl)amino; or-   R₄ and R₅ together with the carbon to which they are attached form a    cycloalkyl ring;-   R₆ is hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl, alkylthiocarbonyl    or unsubstituted or substituted benzyl, whereby the substituents may    each be independent of one another and are selected from the group    consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio,    haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl,    haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl,    haloalkylsulfonyl, SF₅, alkylamino, di(alkyl)amino;-   R₇ is hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl,    alkylthiocarbonyl, unsubstituted or substituted aryl, including    phenyl and naphthyl, wherein the substituents may each be    independent of one another and are selected from the group    consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio,    haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl,    haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl,    SF₅, alkylamino, di(alkyl)amino; unsubstituted or substituted    heteroaryl, including quinolyl, wherein the substituents may each be    independent of one another and are selected from the group    consisting of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio,    haloalkylthio, arylthio, alkoxy, haloalkoxy, alkylcarbonyl,    haloalkylcarbonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl,    SF₅, alkylamino, di(alkyl)amino;    P is C—R₁ or N;    Q is C—R₂ or N;    V is C—R₈ or N;    W is C—R₈ or N;    X is C—R₉ or N;    Y is C—R₁₁ or N;    T is O, S or NH;    Z is a direct bond, C(O), C(S) or S(O)_(p);    a is 1, 2 or 3; and    p is 1 or 2.

It is an object of the present invention to provide new pesticidalcompounds of the thioamide derivatives of formula (I) and (Ia) togetherwith processes for their preparation.

A second object of the present invention is to provide pesticidalcompositions and pesticidal methods of use of the pesticidal thioamidederivatives of formula (I) and (Ia) in the field of pest control whichare well tolerated by warm-blooded species, fish and plants, includingin particular for controlling endo- and ectoparasites which parasitizeanimals.

Another object of the present invention is to provide compounds withhigh activity and improved safety to the user and the environment, whichare obtained by optimization of chemical, physical and biologicalproperties such as solubility, melting point, stability, electronic andsteric parameters, and the like.

For the purposes of this application, unless otherwise stated in thespecification, the following terms have the definitions cited below:

(1) Alkyl refers to both straight and branched carbon chains; referencesto individual alkyl groups are specific for the straight chain (e.g.butyl=n-butyl). In one embodiment of alkyl, the number of carbons atomsis 1-20, in another embodiment of alkyl, the number of carbon atoms is1-8 carbon atoms and in yet another embodiment of alkyl, the number ofcarbon atoms is 1-4 carbon atoms. Other ranges of carbon numbers arealso contemplated depending on the location of the alkyl moiety on themolecule;(2) Alkenyl refers to both straight and branched carbon chains whichhave at least one carbon-carbon double bond. In one embodiment ofalkenyl, the number of double bonds is 1-3, in another embodiment ofalkenyl, the number of double bonds is one. In one embodiment ofalkenyl, the number of carbons atoms is 2-20, in another embodiment ofalkenyl, the number of carbon atoms is 2-8 and in yet another embodimentof alkenyl, the number of carbon atoms is 2-4. Other ranges ofcarbon-carbon double bonds and carbon numbers are also contemplateddepending on the location of the alkenyl moiety on the molecule;(3) Alkynyl refers to both straight and branched carbon chains whichhave at least one carbon-carbon triple bond. In one embodiment ofalkynyl, the number of triple bonds is 1-3; in another embodiment ofalkynyl, the number of triple bonds is one. In one embodiment ofalkynyl, the number of carbons atoms is 2-20, in another embodiment ofalkynyl, the number of carbon atoms is 2-8 and in yet another embodimentof alkynyl, the number of carbon atoms is 2-4. Other ranges ofcarbon-carbon double bonds and carbon numbers are also contemplateddepending on the location of the alkenyl moiety on the molecule;(4) Aryl refers to a C₆-C₁₄ aromatic carbocyclic ring structure having asingle ring or multiple fused rings. Aryl groups include, but are notlimited to, phenyl, biphenyl, and naphthyl. In some embodiments arylincludes tetrahydronaphthyl, phenylcyclopropyl and indanyl. Aryl groupsmay be unsubstituted or substituted by one or more moieties selectedfrom halogen, cyano, nitro, hydroxy, mercapto, amino, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl,halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy,haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy,cycloalkenyloxy, halocycloalkoxy, halocycloalkenyloxy, alkylthio,haloalkylthio, arylthio, cycloalkylthio, halocycloalkylthio,alkylsulfinyl, alkenylsulfinyl, alkynyl-sulfinyl, haloalkylsulfinyl,haloalkenylsulfinyl, haloalkynylsulfinyl, alkylsulfonyl,alkenylsulfonyl, alkynylsulfonyl, haloalkyl-sulfonyl,haloalkenylsulfonyl, haloalkynylsulfonyl, alkylcarbonyl,haloalkylcarbonyl, alkylamino, alkenylamino, alkynylamino,di(alkyl)amino, di(alkenyl)-amino, di(alkynyl)amino, or SF₅.(5) Alkoxy refers to —O-alkyl, wherein alkyl is as defined in (1);(6) Alkanoyl refers to formyl (—C(═O)H) and —C(═O)-alkyl, wherein alkylis as defined in (1);(7) Alkanoyloxy refers to —O—C(═O)-alkyl, wherein alkanoyl is as definedin (6);(8) Alkanoylamino refers to —NH₂—C(═O)-alkyl, wherein alkanoyl is asdefined in (6) and the amino (NH₂) moiety can be substituted by alkyl asdefined in (1);(9) Aminocarbonyl refers to —NH₂—C(═O), wherein the amino (NH₂) moietycan be substituted by alkyl as defined in (1);(10) Alkoxycarbonyl refers to —C(═O)—O-alkyl, wherein alkoxy is asdefined in (5);(11) Alkenoyl refers to —C(═O)-alkenyl, wherein alkenyl is as defined in(2);(12) Alkynoyl refers to —C(═O)-alkynyl, wherein alkynyl is as defined in(3);(13) Aroyl refers to —C(═O)-aryl, wherein aryl is as defined above;(14) Cyclo as a prefix (e.g. cycloalkyl, cycloalkenyl, cycloalkynyl)refers to a saturated or unsaturated cyclic ring structure having fromthree to eight carbon atoms in the ring the scope of which is intendedto be separate and distinct from the definition of aryl above. In oneembodiment of cyclo, the range of ring sizes is 4-7 carbon atoms; inanother embodiment of cyclo the range of ring sizes is 3-4. Other rangesof carbon numbers are also contemplated depending on the location of thecyclo-moiety on the molecule;(15) Halogen means the atoms fluorine, chlorine, bromine and iodine. Thedesignation of “halo” (e.g. as illustrated in the term haloalkyl) refersto all degrees of substitutions from a single substitution to a perhalosubstitution (e.g. as illustrated with methyl as chloromethyl (—CH₂Cl),dichloromethyl (—CHCl₂), trichloromethyl (—CCl₃));(16) Heterocycle, heterocyclic or heterocyclo refer to fully saturatedor unsaturated, cyclic groups, for example, 4 to 7 membered monocyclic,7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring systems,which have at least one heteroatom in at least one carbonatom-containing ring. Each ring of the heterocyclic group containing aheteroatom may have 1, 2, 3 or 4 heteroatoms selected from nitrogenatoms, oxygen atoms and/or sulfur atoms, where the nitrogen and sulfurheteroatoms may optionally be oxidized and the nitrogen heteroatoms mayoptionally be quaternized. The heterocyclic group may be attached at anyheteroatom or carbon atom of the ring or ring system.(17) Heteroaryl refers to a monovalent aromatic group of from 1 to 15carbon atoms, preferably from 1 to 10 carbon atoms, having one or moreoxygen, nitrogen, and sulfur heteroatoms within the ring, preferably 1to 4 heteroatoms, or 1 to 3 heteroatoms. The nitrogen and sulfurheteroatoms may optionally be oxidized. Such heteroaryl groups can havea single ring (e.g., pyridyl or furyl) or multiple fused rings providedthat the point of attachment is through a heteroaryl ring atom.Preferred heteroaryls include pyridyl, piridazinyl, pyrimidinyl,triazinyl, pyrrolyl, quinolinyl, isoquinolinyl, quinazolinyl,quinoxalinyl, furanyl, thiophenyl, furyl, imidazolyl, oxazolyl,isoxazolyl, isothiazolyl, pyrazolyl, benzofuranyl, and benzothiophenyl.Heteroaryl rings may be unsubstituted or substituted by one or moremoieties as described for aryl above.

Exemplary monocyclic heterocyclic or heteroaryl groups also includepyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolinyl,imidazolidinyl, oxazolidinyl, isoxazolinyl, thiazolyl, thiadiazolyl,thiazolidinyl, isothiazolidinyl, tetrahydrofuryl, thienyl, oxadiazolyl,piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl,2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl,pyrazinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl,thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane andtetrahydro-1,1-dioxothienyl, triazolyl, and the like.

Exemplary bicyclic heterocyclic or heteroaryl groups include indolyl,benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl,quinuclidinyl, tetra-hydroisoquinolinyl, isoquinolinyl, benzimidazolyl,benzopyranyl, indolizinyl, benzofuryl, chromonyl, coumarinyl,benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl,furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl] orfuro[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as3,4-dihydro-4-oxo-quinazolinyl), tetrahydroquinolinyl and the like.

Exemplary tricyclic heterocyclic or heteroaryl groups includecarbazolyl, benzidolyl, phenanthrolinyl, acridinyl, phenanthridinyl,xanthenyl and the like.

Unless otherwise specifically noted or apparent by context, “activeagent” or “active ingredient” or “therapeutic agent” as used in thisspecification, means a arylazol-2-yl-methylthiamide amido compound ofthe invention.

The compounds of the invention also are intended to encompass saltforms, racemic mixtures, specific stereoisomers, crystalline andamorphous forms of the compound.

It is further noted that the invention does not intend to encompasswithin the scope of the invention any previously disclosed product,process of making the product or method of using the product, whichmeets the written description and enablement requirements of the USPTO(35 U.S.C. 112, first paragraph) or the EPO (Article 83 of the EPC),such that applicant(s) reserve the right and hereby disclose adisclaimer of any previously described product, method of making theproduct or process of using the product.

It is noted that in this disclosure and particularly in the claimsand/or paragraphs, terms such as “comprises”, “comprised”, “comprising”and the like can have the meaning attributed to it in U.S. patent law;e.g., they can mean “includes”, “included”, “including”, and the like;and that terms such as “consisting essentially of” and “consistsessentially of” have the meaning ascribed to them in U.S. patent law,e.g., they allow for elements not explicitly recited, but excludeelements that are found in the prior art or that affect a basic or novelcharacteristic of the invention.

These and other embodiments are disclosed or are apparent from andencompassed by, the following Detailed Description.

DETAILED DESCRIPTION OF THE INVENTION

A first aspect of the invention provides novel thioamide derivatives offormula (I) and (Ia):

whereinR₁, R₂, R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen,cyano, nitro, halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl, C₁-C₆-alkylthio,halo C₁-C₆-alkylthio, C₁-C₆-alkylsulfinyl, halo C₁-C₆-alkylsulfinyl,C₁-C₆-alkylsulfonyl, halo C₁-C₆-alkylsulfonyl, SF₅, arylthio,C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, unsubstituted or substituted aryl, orunsubstituted or substituted aryloxy including phenoxy, or unsubstitutedor substituted heteroaryl, whereby the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo-C₁-C₆-alkylsulfonyl,SF₅, and methylthioamino;R₃, R₄ and R₅, independently of one another, are hydrogen, halogen,C₁-C₆-alkyl, halo-C₁-C₆-alkyl; C₃-C₇-cycloalkyl that is eitherunsubstituted or substituted, whereby the substituents may each beindependent of one another and are selected from the group consisting ofhalogen and C₁-C₆-alkyl; and aryl that is either unsubstituted orsubstituted, whereby the substituents may each be independent of oneanother and are selected from the group consisting of cyano, nitro,halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,halo-C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino, anddi(C₁-C₆-alkyl)amino;or R₄ and R₅ together signify C₂-C₆-alkylene;R₆ is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,C₁-C₆-alkylcarbonyl, C₁-C₆-alkylthiocarbonyl or benzyl that is eitherunsubstituted or substituted, whereby the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo-C₁-C₆-alkylsulfonyl,SF₅, C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino;R₇ is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylthiocarbonyl or aryl, including phenyl and naphthyl, that iseither unsubstituted or substituted, whereby the substituents may eachbe independent of one another and are selected from the group consistingof cyano, nitro, halogen, C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino,and di(C₁-C₆-alkyl)amino; heteroaryl, including quinolyl, that is eitherunsubstituted or substituted, whereby the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino,and di(C₁-C₆-alkyl)amino;P is C—R₁ or N;Q is C—R₂ or N;V is C—R₈ or N;W is C—R₈ or N;X is C—R₁₀ or N;Y is C—R₁₁ or N;Z is a direct bond, C(O), C(S) or S(O)_(p);T is independently O, S or N;a is 1, 2 or 3; andp is 1 or 2.

In one embodiment of the first aspect of the invention, compounds offormula (I) above are compounds wherein:

-   P and Q are N;-   V is C—R₈;-   W is C—R₉;-   X is C—R₁₀;-   Y is C—R₁₁;-   R₈, R₉, R₁₀ and R₁₁, independently of one another, are cyano, nitro,    halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl, C₁-C₆-alkylthio, halo    C₁-C₆-alkylthio, C₁-C₆-alkylsulfinyl, halo C₁-C₆-alkylsulfinyl,    C₁-C₆-alkylsulfonyl, halo C₁-C₆-alkylsulfonyl, SF₅, arylthio,    C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy, halo-C₁-C₆-alkoxy,    C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,    di(C₁-C₆-alkyl)amino, unsubstituted or substituted aryl or    unsubstituted or substituted phenoxy, whereby the substituents may    each be independent of one another and are selected from the group    consisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,    C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,    halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,    C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,    halo-C₁-C₆-alkylsulfonyl, SF₅, and methylthioamino;-   R₃, R₄ and R₆ are H;-   R₅ is methyl or C₁-C₃-alkyl;-   R₇ is unsubstituted or substituted phenyl wherein the substituents    may each be independent of one another and are selected from the    group consisting of cyano, nitro, halogen, C₁-C₆-alkyl,    halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio,    C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,    halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅,    C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; unsubstituted or    substituted heteroaryl, wherein the substituents may each be    independent of one another and are selected from the group    consisting of cyano, nitro, halogen, C₁-C₆-alkyl, C₁-C₆-alkylthio,    halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,    C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅,    C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino;    -   or    -   unsubstituted or substituted naphthyl or quinolyl, wherein the        substituents may each be independent of one another and are        selected from the group consisting of cyano, nitro, halogen,        C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio,        C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,        halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,        halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,        and di(C₁-C₆-alkyl)amino;-   Z is a direct bond, C(O), C(S) or S(O)_(p); and-   a is 1.

In yet another embodiment of the first aspect of the invention,compounds of formula (I) or (Ia) above are compounds wherein:

-   P and Q are N;-   V is C—R₈;-   W is C—R₉;-   X is C—R₁₀;-   Y is C—R₁₁;-   R₈, R₉, R₁₀ and R₁₁, independently of one another, are cyano, nitro,    halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl, C₁-C₆-alkylthio, halo    C₁-C₆-alkylthio, C₁-C₆-alkylsulfinyl, halo C₁-C₆-alkylsulfinyl,    C₁-C₆-alkylsulfonyl, halo C₁-C₆-alkylsulfonyl, SF₅, arylthio,    C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy, halo-C₁-C₆-alkoxy,    C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,    di(C₁-C₆-alkyl)amino, unsubstituted or substituted aryl or    unsubstituted or substituted phenoxy, whereby the substituents may    each be independent of one another and are selected from the group    consisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,    C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,    halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,    halo-C₁-C₆-alkylsulfonyl, SF₅, and methylthioamino;-   R₃, R₄ and R₆ are H;-   R₅ is methyl or C₁-C₃-alkyl;-   R₇ is unsubstituted or substituted phenyl wherein the substituents    may each be independent of one another and are selected from the    group consisting of cyano, nitro, halogen, C₁-C₆-alkyl,    halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio,    C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,    halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅,    C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; unsubstituted or    substituted heteroaryl, wherein the substituents may each be    independent of one another and are selected-   from the group consisting of cyano, nitro, halogen, C₁-C₆-alkyl,    C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,    halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,    C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,    SF₅, alkylamino, and di(C₁-C₆-alkyl)amino;-   Z is C(O);-   T is independently O, S or N; and-   a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) or (Ia) above are compounds wherein:

-   P and Q is N;-   V is C—R₈;-   W is C—R₉;-   X is C—R₁₀;-   Y is C—R₁₁;-   R₈, R₉, R₁₀ and R₁₁, independently of one another, are cyano, nitro,    halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl, C₁-C₆-alkylthio, halo    C₁-C₆-alkylthio, C₁-C₆-alkylsulfinyl, halo C₁-C₆-alkylsulfinyl,    C₁-C₆-alkylsulfonyl, halo C₁-C₆-alkylsulfonyl, SF₅, arylthio,    C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy, halo-C₁-C₆-alkoxy,    C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,    di(C₁-C₆-alkyl)amino, unsubstituted or substituted aryl or    unsubstituted or substituted phenoxy, whereby the substituents may    each be independent of one another and are selected from the group    consisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,    C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,    halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,    halo-C₁-C₆-alkylsulfonyl, SF₅, and methylthioamino;-   R₃, R₄ and R₆ are H;-   R₅ is methyl;-   R₇ is unsubstituted or substituted phenyl wherein the substituents    may each be independent of one another and are selected from the    group consisting of cyano, nitro, halogen, C₁-C₆-alkyl,    halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio,    C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,    halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,    halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅,    C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; unsubstituted or    substituted heteroaryl, wherein the substituents may each be    independent of one another and are selected-   from the group consisting of cyano, nitro, halogen, C₁-C₆-alkyl,    C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,    halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,    C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,    SF₅, C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino;-   Z is C(O)-   a is 1;-   m and n are independently 0 or 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) or (Ia) above are compounds wherein:

R₁, R₂, R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen,cyano, halogen, C₁-C₆-alkyl, halomethyl or methylthioamino;

R₃, R₄ and R₆ are H;

R₅ is methyl or C₁-C₃-alkyl;

P is C—R₁ or N;

Q is C—R₂ or N;

V is C—R₈ or N;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁ or N;

T is O or S;

Z is C(O); and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) above are compounds wherein:

R₁, R₂, R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen,cyano, chloro, bromo, methyl or trifluoromethyl;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is C—R₁ or N;

Q is C—R₂ or N;

V is C—R₈ or N;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁ or N;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, anda is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) above are compounds wherein:

R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, cyano,chloro, bromo, methyl or trifluoromethyl;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is N;

Q is N;

V is C—R₈;

W is C—R₈;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalogen, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, C₁-C₆-alkoxy, andhalo-C₁-C₆-alkoxy, and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) above are compounds wherein:

R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, cyano,chloro, bromo, methyl, or trifluoromethyl;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is N;

Q is N;

V is C—R₈;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

In another embodiment of the first aspect of the invention, compounds offormula (I) above are compounds wherein:

R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, cyano,chloro, bromo, methyl or trifluoromethyl;

R₃, R₄ and R₆ are H;

R₂ is H, chloro, bromo or C₁-C₆-alkoxy;

R₅ is methyl;

P is N;

Q is C—R₂;

V is N;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) above are compounds wherein:

R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, chloro,bromo, methyl or trifluoromethyl;

R₃, R₄ and R₆ is H;

R₂ is H, chloro, bromo or C₁-C₆-alkoxy;

R₅ is methyl;

P is N;

is C—R₂;

V is C—R₈;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) above are compounds wherein:

R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, cyano,chloro, bromo, methyl or trifluoromethyl;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is N;

Q is N;

V is C—R₈;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

In another embodiment of the first aspect of the invention, compounds offormula (I) above are compounds wherein:

R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, chloro,bromo or methyl;

R₃, R₄ and R₆ are H;

R₂ is H, chloro, bromo or methoxy;

R₅ is methyl;

P is N;

Q is C—R₂;

V is N;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (I) above are compounds wherein:

R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, chloro,bromo, methyl or trifluoromethyl;

R₃, R₄ and R₆ is H;

R₂ is H, chloro, bromo, methoxy, ethoxy, propoxy or butoxy;

R₅ is methyl;

P is N;

Q is C—R₂;

V is C—R₈;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (Ia) above are compounds wherein:

R₁, R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen,cyano, chloro, trifluoromethyl or methylamino;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is C—R₁ or N;

V is C—R₈ or N;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁ or N;

Z is C(O);

T is O;

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, anda is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (Ia) above are compounds wherein:

R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, cyano,chloro, trifluoromethyl or methylthioamino;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is N;

V is C—R₈;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

T is O;

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalogen, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, C₁-C₆-alkoxy, andhalo-C₁-C₆-alkoxy, and

a is 1.

In still another embodiment of the first aspect of the invention,compounds of formula (Ia) above are compounds wherein:

R₈, R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, cyano,chloro, trifluoromethyl or methylthioamino;

R₃, R₄ and R₆ is H;

R₅ is methyl;

P is N;

V is C—R₈;

W is C—R₉;

X is C—R₁₀;

Y is C—R₁₁;

Z is C(O);

T is O;

R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and

a is 1.

Tables 1, 2 and 3 below provide additional particularly preferredcompounds of the invention of formula (Ib), (Ic) and (Id) that areencompassed by formula (I).

TABLE 1

Com- pound # R R₅ R₈ R₉ R₁₀ R₁₁ 1.001 OCF₃ Me H Cl H H 1.002 CF₃ Me H ClH H 1.003 SCF₃ Me H Cl H H 1.004 OCF₃ Me H H H H 1.005 SCF₃ Me H H H H1.006 OCF₃ Me H Me H H 1.007 SCF₃ Me H Me H H 1.008 OCF₃ Me H CF₃ H H1.009 SCF₃ Me H CF₃ H H 1.010 OCF₃ Me H Cl Cl H 1.011 SCF₃ Me H Cl Cl H1.012 OCF₃ Me Cl H Cl H 1.013 SCF₃ Me Cl H Cl H 1.014 OCF₃ Me Cl H CF₃ H1.015 SCF₃ Me Cl H CF₃ H 1.016 OCF₃ Me H CN H H 1.017 SCF₃ Me H CN H H1.018 OCF₃ Me CF₃ H CF₃ H 1.019 SCF₃ Me CF₃ H CF₃ H 1.020 OCF₃ Me H Br HH 1.021 SCF₃ Me H Br H H 1.022 SOCF₃ Me H CN H H 1.023 SOCF₃ Me Cl H CF₃H 1.024 SOCF₃ Me Cl H Cl H 1.025 SO₂CF₃Me Cl H Cl H H 1.026 SO₂CF₃Me HCF₃ H H H 1.027 SO₂CF₃Me H CN H H H 1.028 SO₂CF₃Me Cl H CF₃ H H 1.029SO₂CF₃Me H H H H H 1.030 SO₂CF₃Me H Me H H H 1.031 SO₂CF₃Me H 01 H H H1.032 OPh Me H Cl H H 1.033 OCF₃ Me Me H Cl H 1.034 SCF₃ Me Me H Cl H1.035 OCF₃ Me H OCF₃ H H 1.036 SCF₃ Me H OCF₃ H H 1.037 OCF₃ Me CF₃ H ClH 1.038 SCF₃ Me CF₃ H Cl H 1.039 OPh Me Me H Cl H 1.040 OCF₃ Me H Cl MeH 1.041 SCF₃ Me H Cl Me H 1.042 OPh Me CF₃ H Cl H 1.043 OCF₃ Me Cl H H H1.044 SCF₃ Me Cl H H H 1.045 OPh Me Cl H H H 1.046 Ph Me Cl H Cl H 1.047OCF₃ Et H Cl H H 1.048 SCF₃ Et H Cl H H 1.049 OCF₃ CH₂CH(CH₃)₂ H Cl H H1.050 SCF₃ CH₂CH(CH₃)₂ H Cl H H 1.051 OCF₃ t-Bu H Cl H H 1.052 SCF₃ t-BuH Cl H H 1.053 t-Bu Me Cl H Cl H 1.054 OCF₃ Me CN H CF₃ H 1.055 SCF₃ MeCN H CF₃ H 1.056 OCF₃ Me CF₃ H CN H 1.057 OCF₃ Me Br Cl H H 1.058 OCF₃CH₂OH H Cl H H 1.059 SCF₃ CH₂OH H Cl H H 1.060 OCF₃ Me Br H Cl H 1.061OCF₃ CH₂SMe H Cl H H 1.062 OCF₃ CH₂OMe H Cl H H 1.063 OCF₃ CHOSO₂Me H ClH H 1.064 OCF₃ Me Cl Cl H Cl 1.065 SCF₃ Me Cl Cl H Cl 1.066 SCF₃ Me CF₃H CN H 1.067 OCF₃ Me CN H Cl H 1.068 OCF₃ Me p-Ph-CF₃ H Cl H 1.069CHFCF₃ Me Cl Cl H Cl 1.070 OCF₃ Me Cl H OMe H 1.071 SCF₃ Me Cl H OMe H1.072 OCF₃ Me H OMe H H 1.073 SCF₃ Me H OMe H H 1.074 OCF₃ Me CH₂NH₂ HCl H 1.075 OCF₃ Me Vinyl H Cl H 1.076 SCF₃ Me Vinyl H Cl H 1.077 OCF₃ MeCH(OH)CH₂OH H Cl H 1.078 OCF₃ Me CH(F)CH₂F H Cl H 1.079 OCF₃ Me Formyl HCl H 1.080 OCF₃ Me CH₂NMe₂ H Cl H 1.081 OCF₃ Me CH₂CH H Cl H 1.082 OCF₃Me CO₂H H Cl H 1.083 OCF₃ Me Br Cl H Br 1.084 OCF₃ Me CO₂Me H Cl H 1.085SCF₃ Me Br Cl H Br 1.086 OCF₃ Me Br Cl H Cl 1.087 SCF₃ Me Br Cl H Cl1.088 OCF₃ Me Br Cl Br Cl 1.089 SCF₃ Me Br Cl Br Cl 1.090 OCF₃ Me F Cl HCl 1.091 SCF₃ Me F Cl H Cl 1.092 OCF₃ Me Me Cl H Me 1.093 SCF₃ Me Me ClH Me 1.094 OCF₃ Me F Br H Me 1.095 SCF₃ Me F Br H Me V = C—R₈; W = C—R₉;X = C—R₁₀; Y = C—R₁₁; Q = P = N; R₃ = R₄ = R₆ = H; a = 1; R₅ = CH₃; Z =C(O); R₇ = p-phenyl-R

TABLE 2

Com- pound # R R₂ R₈ R₉ R₁₀ R₁₁ 2.001 OCF₃ H H NO₂ H H 2.002 SCF₃ H HNO₂ H H 2.003 OCF₃ H H Cl H Cl 2.004 OPh H H Cl H Cl 2.005 SCF₃ H H Cl HCl 2.006 OCF₃ H H Cl H Me 2.007 SCF₃ H H Cl H Me 2.008 OCF₃ OMe H H Cl H2.009 SCF₃ OMe H H Cl H 2.010 OCF₃ Me H Cl H Cl 2.011 SCF₃ Me H Cl H Cl2.012 OCF₃ OMe H Cl H H 2.013 SCF₃ OMe H Cl H H 2.014 OCF₃ OEt H Cl H H2.015 SCF₃ OEt H Cl H H 2.016 OCF₃ OMe H H H H 2.017 OCF₃ O(CH₂)₂OMe H HCl H 2.018 OCF₃ O(CH₂)₂NMe₂ H H Cl H 2.019 SCF₃ OMe H Cl H Cl 2.020 OCF₃OMe H Cl H Cl 2.021 OCF₃ OMe Cl H Cl H 2.022 SCF₃ OMe Cl H Cl H 2.023OCF₃ OMe H H Br H 2.024 SCF₃ OMe H H Br H 2.025 OCF₃ OMe H H CF₃ H 2.026SCF₃ OMe H H CF₃ H 2.027 OCF₃ OEt H H Cl H 2.028 SCF₃ OEt H H Cl H 2.029OCF₃ O-n-Pr H H Cl H 2.030 SCF₃ O-n-Pr H H Cl H 2.031 OCF₃ O-n-Bu H H ClH 2.032 OCF₃ OMe H H CO₂Me H 2.033 OCF₃ OMe H H NO₂ H 2.034 OCF₃ OMe H HNH₂ H 2.035 OCF₃ OMe H H NHAc H 2.036 OCF₃ OMe H H CONH₂ H 2.037 OCF₃ HH H Cl H 2.038 SCF₃ H H H Cl H 2.039 OCF₃ Cl H H Cl Cl 2.040 OCF₃ H Cl HCl H 2.041 SCF₃ H Cl H Cl H 2.042 OCF₃ Br H H Cl H 2.043 OCF₃ H H H ClBr 2.044 OCF₃ Cl H H Cl H 2.045 OCF₃ H H H Cl Cl 2.046 OCF₃ Br Cl H ClBr 2.047 OCF₃ H Cl H Cl Br 2.048 OCF₃ H Cl H Cl Cl 2.049 SCF₃ H Cl H ClCl 2.050 OCF₃ Me H H Cl H V = C—R₈; W = C—R₉; X = C—R₁₀; Y = C—R₁₁; Q =C—R₂; P = N; R₃ = R₄ = R₆ = H; a = 1; R₅ = CH₃; Z = C(O); R₇ =p-phenyl-R

TABLE 3

Compound # R Q R₉ R₁₀ R₁₁ 3.001 OCF₃ C—OMe H Cl H 3.002 SCF₃ C—OMe H ClH 3.003 OCF₃ N H Br Me 3.004 SCF₃ N H Br Me 3.005 OCF₃ C—H H Cl H 3.006SCF₃ C—H H Cl H 3.007 OCF₃ C—OMe H Br Me 3.008 OCF₃ C—OMe H Cl Me 3.009OCF₃ C—H H Br Me 3.010 OCF₃ C—H H Cl Me 3.011 OCF₃ C—H H Br H 3.012 SCF₃C—H H Br H 3.013 OCF₃ C—H H Cl Cl 3.014 SCF₃ C—H H Cl Cl 3.015 OCF₃ C—HH Br Cl 3.016 SCF₃ C—H H Br Cl 3.017 OCF₃ C—Cl H Cl H 3.018 SCF₃ C—Cl HCl H 3.019 OCF₃ C—Br H Cl H 3.020 SCF₃ C—Br H Cl H 3.021 OCF₃ C—H H ClBr 3.022 SCF₃ C—H H Cl Br 3.023 SCF₃ C—H H Br Me V = N; W = C—R₉; X =C—R₁₀; Y = C—R₁₁; Q = C—R₂ where R₂ is as defined for formula (I) above;P = N; R₃ = R₄ = R₆ = H; a = 1; R₅ = CH₃; Z = C(O); R₇ = p-phenyl-RFormulations and Administration for Pharmaceutical/Veterinary Use

Another aspect of the invention is the formation of antiparasiticidalcompositions which comprise the thioamide compounds of the invention.The composition of the invention can also be in a variety of forms whichinclude, but are not limited to, oral formulations, injectableformulations, and topical, dermal or subdermal formulations.

The composition of the invention may be in a form suitable for oral use,for example, as baits (see, e.g., U.S. Pat. No. 4,564,631), dietarysupplements, troches, lozenges, chewables, tablets, hard or softcapsules, emulsions, aqueous or oily suspensions, aqueous or oilysolutions, oral drench formulations, dispersible powders or granules,syrups or elixirs, enteric formulations or pastes. Compositions intendedfor oral use may be prepared according to any method known in the artfor the manufacture of pharmaceutical compositions and such compositionsmay contain one or more agents selected from the group consisting ofsweetening agents, bittering agents, flavoring agents, coloring agentsand preserving agents in order to provide pharmaceutically elegant andpalatable preparations.

Tablets may contain the active ingredient in admixture with non-toxic,pharmaceutically acceptable excipients which are suitable for themanufacture of tablets. These excipients may be, for example, inertdiluents, such as calcium carbonate, sodium carbonate, lactose, calciumphosphate or sodium phosphate; granulating and disintegrating agents,for example, corn starch, or alginic acid; binding agents, for examplestarch, gelatin or acacia, and lubricating agents, for example,magnesium stearate, stearic acid or talc, the tablets may be uncoated orthey may be coated by known techniques to delay disintegration andabsorption in the gastrointestinal tract and thereby provide a sustainedaction over a longer period. For example, a time delay material such asglyceryl monostearate or glyceryl distearate may be employed. They mayalso be coated by the technique described in U.S. Pat. Nos. 4,256,108;4,166,452; and 4,265,874 (incorporated herein by reference) to formosmotic therapeutic tablets for controlled release.

Formulations for oral use may be hard gelatin capsules, wherein theactive ingredient is mixed with an inert solid diluent, for example,calcium carbonate, calcium phosphate or kaolin. Capsules may also besoft gelatin capsules, wherein the active ingredient is mixed with wateror miscible solvents such as propylene glycol, PEGs and ethanol, or anoil medium, for example peanut oil, liquid paraffin, or olive oil.

The compositions of the invention may also be in the form ofoil-in-water or water-in-oil emulsions. The oily phase maybe a vegetableoil, for example, olive oil or arachis oil, or a mineral oil, forexample, liquid paraffin or mixtures of these. Suitable emulsifyingagents may be naturally-occurring phosphatides, for example, soy bean,lecithin, and esters or partial esters derived from fatty acids andhexitol anhydrides, for example, sorbitan monoleate, and condensationproducts of the said partial esters with ethylene oxide, for example,polyoxyethylene sorbitan monooleate. The emulsions may also containsweetening agents, bittering agents, flavoring agents, and/orpreservatives.

In one embodiment of the formulation, the composition of the inventionis in the form of a microemulsion. Microemulsions are well suited as theliquid carrier vehicle. Microemulsions are quaternary systems comprisingan aqueous phase, an oily phase, a surfactant and a cosurfactant. Theyare translucent and isotropic liquids.

Microemulsions are composed of stable dispersions of microdroplets ofthe aqueous phase in the oily phase or conversely of microdroplets ofthe oily phase in the aqueous phase. The size of these microdroplets isless than 200 nm (1000 to 100,000 nm for emulsions). The interfacialfilm is composed of an alternation of surface-active (SA) andco-surface-active (Co-SA) molecules which, by lowering the interfacialtension, allows the microemulsion to be formed spontaneously.

In one embodiment of the oily phase, the oily phase can be formed frommineral or vegetable oils, from unsaturated polyglycosylated glyceridesor from triglycerides, or alternatively from mixtures of such compounds.In one embodiment of the oily phase, the oily phase comprises oftriglycerides; in another embodiment of the oily phase, thetriglycerides are medium-chain triglycerides, for example C₈-C₁₀caprylic/capric triglyceride. In another embodiment of the oily phasewill represent a % v/v range selected from the group consisting of about2 to about 15%; about 7 to about 10%; and about 8 to about 9% v/v of themicroemulsion.

The aqueous phase includes, for example water or glycol derivatives,such as propylene glycol, glycol ethers, polyethylene glycols orglycerol. In one embodiment of the glycol derivatives, the glycol isselected from the group consisting of propylene glycol, diethyleneglycol monoethyl ether, dipropylene glycol monoethyl ether and mixturesthereof. Generally, the aqueous phase will represent a proportion fromabout 1 to about 4% v/v in the microemulsion.

Surfactants for the microemulsion include diethylene glycol monoethylether, dipropylene glycol monomethyl ether, polyglycolyzed C₈-C₁₀glycerides or polyglyceryl-6 dioleate. In addition to these surfactants,the cosurfactants include short-chain alcohols, such as ethanol andpropanol.

Some compounds are common to the three components discussed above, i.e.,aqueous phase, surfactant and cosurfactant. However, it is well withinthe skill level of the practitioner to use different compounds for eachcomponent of the same formulation. In one embodiment for the amount ofsurfactant/cosurfactant, the cosurfactant to surfactant ratio will befrom about 1/7 to about 1/2. In another embodiment for the amount ofcosurfactant, there will be from about 25 to about 75% v/v of surfactantand from about 10 to about 55% v/v of cosurfactant in the microemulsion.

Oily suspensions may be formulated by suspending the active ingredientin a vegetable oil, for example, atachis oil, olive oil, sesame oil orcoconut oil, or in mineral oil such as liquid paraffin. The oilysuspensions may contain a thickening agent, for example, beeswax, hardparaffin or cetyl alcohol. Sweetening agents such as sucrose, saccharinor aspartame, bittering agents, and flavoring agents may be added toprovide a palatable oral preparation. These compositions may bepreserved by the addition of an anti-oxidant such as ascorbic acid, orother known preservatives.

Aqueous suspensions may contain the active material in admixture withexcipients suitable for the manufacture of aqueous suspensions. Suchexcipients are suspending agents, for example, sodiumcarboxymethylcellulose, methylcellulose, hydroxy-propylmethylcellulose,sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia;dispersing or wetting agents may be a naturally-occurring phosphatide,for example lecithin, or condensation products of an alkylene oxide withfatty acids, for example polyoxyethylene stearate, or condensationproducts of ethylene oxide with long chain aliphatic alcohols, forexample, heptadecaethyleneoxycetanol, or condensation products ofethylene oxide with partial esters derived from fatty acids and ahexitol such as polyoxyethylene sorbitol monooleate, or condensationproducts of ethylene oxide, with partial esters derived from fatty acidsand hexitol anhydrides, for example polyethylene sorbitan monooleate.The aqueous suspensions may also contain one or more preservatives, forexample ethyl, or n-propyl, p-hydroxybenzoate, one or more coloringagents, one or more flavoring agents, and one or more sweetening agentsand/or bittering agents, such as those set forth above.

Dispersible powders and granules suitable for preparation of an aqueoussuspension by the addition of water provide the active ingredient inadmixture with a dispersing or wetting agent, suspending agent and oneor more preservatives. Suitable dispersing or wetting agents andsuspending agents are exemplified by those already mentioned above.Additional excipients, for example, sweetening, bittering, flavoring andcoloring agents, may also be present.

Syrups and elixirs may be formulated with sweetening agents, forexample, glycerol, propylene glycol, sorbitol or sucrose. Suchformulations may also contain a demulcent, a preservative, flavoringagent(s) and/or coloring agent(s).

In another embodiment of the invention, the composition can be in pasteform. Examples of embodiments in a paste form include but are notlimited to those described in U.S. Pat. Nos. 6,787,342 and 7,001,889(each of which are incorporated herein by reference). In addition to thecompound(s) of the invention, the paste can also contain fumed silica; aviscosity modifier; a carrier; optionally, an absorbent; and optionally,a colorant, stabilizer, surfactant, or preservative.

The process for preparing a paste formulation comprises the steps of:

(a) dissolving or dispersing the 1-aryl-5-alkyl compound into thecarrier by mixing;

(b) adding the fumed silica to the carrier containing the dissolvedactive compound and mixing until the silica is dispersed in the carrier;

(c) allowing the intermediate formed in (b) to settle for a timesufficient in order to allow the air entrapped during step (b) toescape; and

(d) adding the viscosity modifier to the intermediate with mixing toproduce a uniform paste.

The above steps are illustrative, but not limiting. For example, step(a) can be the last step.

In one embodiment of the formulation, the formulation is a pastecontaining a thioamide compound of the invention, fumed silica, aviscosity modifier, an absorbent, a colorant; and a hydrophilic carrierwhich is triacetin, a monoglyceride, a diglyceride, or a triglyceride.

The paste may also include, but is not limited to, a viscosity modifierselected from the group consisting of PEG 200, PEG 300, PEG 400, PEG600, monoethanolamine, triethanolamine, glycerol, propylene glycol,polyoxyethylene (20) sorbitan mono-oleate (polysorbate 80 or Tween 80),and polyoxamers (e.g., Pluronic L 81); an absorbent selected from thegroup consisting of magnesium carbonate, calcium carbonate, starch, andcellulose and its derivatives; and a colorant selected from the groupconsisting of titanium dioxide iron oxide, and FD&C Blue #1 AluminumLake.

The compositions may be in the form of a sterile injectable aqueous oroleagenous suspension. This suspension may be formulated according tothe known art using those suitable dispersing or wetting agents andsuspending agents which have been mentioned above. The sterileinjectable preparation may also be a sterile injectable solution orsuspension in a non-toxic parenterally-acceptable diluent or solvent,for example, as a solution in 1,3-butane diol. Among the acceptablevehicles and solvents that may be employed are water, Ringers solutionand isotonic sodium chloride solution. Cosolvents such as ethanol,propylene glycol or polyethylene glycols may also be used.Preservatives, such as phenol or benzyl alcohol, may be used.

In addition, sterile, fixed oils are conventionally employed as asolvent or suspending medium. For this purpose any bland fixed oil maybe employed including synthetic mono- or diglycerides. In addition,fatty acids such as oleic acid find use in the preparation ofinjectables.

Topical, dermal and subdermal formulations can include emulsions,creams, ointments, gels, pastes, powders, shampoos, pour-onformulations, ready-to-use formulations, spot-on solutions andsuspensions. Topical application of an inventive compound or of acomposition including at least one inventive compound among activeagent(s) therein, a spot-on composition, can allow for the inventivecompound to be distributed through the glands (e.g. sebaceous glands) ofthe animal and/or allow active agent(s) to achieve a systemic effect(plasma concentration) or throughout the haircoat. When the compound isdistributed throughout glands, the glands can act as a reservoir,whereby there can be a long-lasting, e.g. 1-2 months effect. Spot-onformulations are typically applied in a localized region which refers toan area other than the entire animal. In one embodiment of a localizedregion, the location is between the shoulders. In another embodiment ofa localized region is a stripe, e.g. a stripe from head to tail of theanimal.

Pour-on formulations are described in U.S. Pat. No. 6,010,710,incorporated herein by reference. The pour-on formulations areadvantageously oily, and generally comprise a diluent or vehicle andalso a solvent (e.g. an organic solvent) for the active ingredient ifthe latter is not soluble in the diluent.

Organic solvents that can be used in the invention include but are notlimited to: acetyltributyl citrate, fatty acid esters such as thedimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzylalcohol, butyl diglycol, dimethylacetamide, dimethylformamide,dipropylene glycol n-butyl ether, ethanol, isopropanol, methanol,ethylene glycol monoethyl ether, ethylene glycol monomethyl ether,monomethylacetamide, dipropylene glycol monomethyl ether, liquidpolyoxyethylene glycols, propylene glycol, 2-pyrrolidone (e.g.N-methylpyrrolidone), diethylene glycol monoethyl ether, ethylene glycoland diethyl phthalate, or a mixture of at least two of these solvents.

As vehicle or diluent, mention may be made of plant oils such as, butnot limited to soybean oil, groundnut oil, castor oil, corn oil, cottonoil, olive oil, grape seed oil, sunflower oil, etc.; mineral oils suchas, but not limited to, petrolatum, paraffin, silicone, etc.; aliphaticor cyclic hydrocarbons or alternatively, for example, medium-chain (suchas C8 to C12) triglycerides.

In another embodiment of the invention, an emollient and/or spreadingand/or film-forming agent will be added. One embodiment of the emollientand/or spreading and/or film-forming agent are those agents selectedfrom the group consisting of:

(a) polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinylacetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol,mannitol, glycerol, sorbitol, polyoxyethylenated sorbitan esters;lecithin, sodium carboxymethylcellulose, silicone oils,polydiorganosiloxane oils (such as polydimethylsiloxane (PDMS) oils),for example those containing silanol functionalities, or a 45V2 oil,(b) anionic surfactants such as alkaline stearates, sodium, potassium orammonium stearates; calcium stearate, triethanolamine stearate; sodiumabietate; alkyl sulphates (e.g. sodium lauryl sulphate and sodium cetylsulphate); sodium dodecylbenzenesulphonate, sodiumdioctylsulphosuccinate; fatty acids (e.g. those derived from coconutoil),(c) cationic surfactants such as water-soluble quaternary ammonium saltsof formula N⁺R′R″R′″R″″, Y⁻ in which the radicals R are optionallyhydroxylated hydrocarbon radicals and Y⁻ is an anion of a strong acidsuch as the halide, sulphate and sulphonate anions;cetyltrimethylammonium bromide is among the cationic surfactants whichcan be used,(d) amine salts of formula N⁺R′R″R′″ in which the radicals R areoptionally hydroxylated hydrocarbon radicals; octadecylaminehydrochloride is among the cationic surfactants which can be used,(e) nonionic surfactants such as sorbitan esters, which are optionallypolyoxyethylenated (e.g. polysorbate 80), polyoxyethylenated alkylethers; polyoxypropylated fatty alcohols such as polyoxypropylene-styrolether; polyethylene glycol stearate, polyoxyethylenated derivatives ofcastor oil, polyglycerol esters, polyoxyethylenated fatty alcohols,polyoxyethylenated fatty acids, copolymers of ethylene oxide andpropylene oxide,(f) amphoteric surfactants such as the substituted lauryl compounds ofbetaine; or(g) a mixture of at least two of these agents.

The solvent will be used in proportion with the concentration of thethioamide compound of formula (I) or (Ia) and its solubility in thissolvent. It will be sought to have the lowest possible volume. Thevehicle makes up the difference to 100%.

In one embodiment of the amount of emollient, the emollient is used in aproportion selected from the group consisting of from 0.1 to 10% and0.25 to 5%, by volume.

In another embodiment of the invention, the composition can be inready-to-use solution form as is described in U.S. Pat. No. 6,395,765,incorporated herein by reference. In addition to the thioamide compoundof formula (I) or (Ia), the ready-to-use solution can contain acrystallization inhibitor, an organic solvent and an organic co-solvent.

In one embodiment of the amount of crystallization inhibitor, thecrystallization inhibitor can be present in a proportion selected fromthe group consisting of about 1 to about 20% (w/v) and about 5 to about15%. In another embodiment of the amount of crystallization inhibitor,the amount corresponds to the test in which 0.3 ml of a solutioncomprising 10% (w/v) of the thioamide compound in the liquid carrier and10% of the inhibitor are deposited on a glass slide at 20° C. andallowed to stand for 24 hours. The slide is then observed with the nakedeye. Acceptable inhibitors are those whose addition provides for few(e.g. less than ten crystals) or no crystal.

The organic solvent has a dielectric constant of a range selected fromthe group consisting of between about 10 and 35 and between about 20 and30, the content of this organic solvent in the overall compositionrepresenting the complement to 100% of the composition; and the organicco-solvent having a boiling point selected from the ranges consisting ofbelow 100° C., and below 80° C., and having a dielectric constant of arange selected from the group consisting of between about 10 and 40 andbetween about 20 and 30; this co-solvent may be present in thecomposition in a organic co-solvent/organic solvent weight/weight (W/W)ratio of between about 1/15 and 1/2. The solvent is volatile so as toact as a drying promoter, and is miscible with water and/or with theorganic solvent.

The formulation can also comprise an antioxidizing agent intended toinhibit oxidation in air, this agent being present in a proportionselected from a range consisting of about 0.005 to about 1% (w/v) andabout 0.01 to about 0.05%.

Crystallization inhibitors which are useful for the invention includebut are not limited to:

(a) polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinylacetate and of vinylpyrrolidone, polyethylene glycols, benzyl alcohol,mannitol, glycerol, sorbitol or polyoxyethylenated esters of sorbitan;lecithin or sodium carboxymethylcellulose; or acrylic derivatives, suchas methacrylates and others;(b) anionic surfactants, such as alkaline stearates (e.g. sodium,potassium or ammonium stearate); calcium stearate or triethanolaminestearate; sodium abietate; alkyl sulphates, which include but are notlimited to sodium lauryl sulphate and sodium cetyl sulphate; sodiumdodecylbenzenesulphonate or sodium dioctyl sulphosuccinate; or fattyacids (e.g. coconut oil);(c) cationic surfactants, such as water-soluble quaternary ammoniumsalts of formula N⁺R′R″R′″R″″Y⁻, in which the R radicals are identicalor different optionally hydroxylated hydrocarbon radicals and Y⁻ is ananion of a strong acid, such as halide, sulphate and sulphonate anions;cetyltrimethylammonium bromide is one of the cationic surfactants whichcan be used;(d) amine salts of formula N⁺R′R″R′″, in which the R radicals areidentical or different optionally hydroxylated hydrocarbon radicals;octadecylamine hydrochloride is one of the cationic surfactants whichcan be used;(e) non-ionic surfactants, such as optionally polyoxyethylenated estersof sorbitan, e.g. Polysorbate 80, or polyoxyethylenated alkyl ethers;polyethylene glycol stearate, polyoxyethylenated derivatives of castoroil, polyglycerol esters, polyoxyethylenated fatty alcohols,polyoxyethylenated fatty acids or copolymers of ethylene oxide and ofpropylene oxide;(f) amphoteric surfactants, such as substituted lauryl compounds ofbetaine; or(g) a mixture of at least two of the compounds listed in (a)-(f) above.In one embodiment of the crystallization inhibitor, a crystallizationinhibitor pair will be used. Such pairs include, for example, thecombination of a film-forming agent of polymeric type and of asurface-active agent. These agents will be selected from the compoundsmentioned above as crystallization inhibitor.

In one embodiment of the film-forming agent, the agents are of thepolymeric type which include but are not limited to the various gradesof polyvinylpyrrolidone, polyvinyl alcohols, and copolymers of vinylacetate and of vinylpyrrolidone.

In one embodiment of the surface-active agents, the agents include butare not limited to those made of non-ionic surfactants; in anotherembodiment of the surface active agents, the agent is apolyoxyethylenated esters of sorbitan and in yet another embodiment ofthe surface-active agent, the agents include the various grades ofpolysorbate, for example Polysorbate 80.

In another embodiment of the invention, the film-forming agent and thesurface-active agent can be incorporated in similar or identical amountswithin the limit of the total amounts of crystallization inhibitormentioned elsewhere.

The pair thus constituted secures, in a noteworthy way, the objectivesof absence of crystallization on the coat and of maintenance of thecosmetic appearance of the skin or fur, that is to say without atendency towards sticking or towards a sticky appearance, despite thehigh concentration of active material.

In one embodiment of the antioxidizing agents, the agents are thoseconventional in the art and include but is not limited to butylatedhydroxyanisole, butylated hydroxytoluene, ascorbic acid, sodiummetabisulphite, propyl gallate, sodium thiosulphate or a mixture of notmore than two of them.

The formulation adjuvants discussed above are well known to thepractitioner in this art and may be obtained commercially or throughknown techniques. These concentrated compositions are generally preparedby simple mixing of the constituents as defined above; advantageously,the starting point is to mix the active material in the main solvent andthen the other ingredients or adjuvants are added.

The volume applied can be of the order of about 0.3 to about 1 ml. Inone embodiment for the volume, the volume is on the order of about 0.5ml, for cats and on the order of about 0.3 to about 3 ml for dogs,depending on the weight of the animal.

In another embodiment of the invention, application of a spot-onformulation according to the present invention can also providelong-lasting and broad-spectrum efficacy when the solution is applied tothe mammal or bird. The spot-on formulations provide for topicaladministration of a concentrated solution, suspension, microemulsion oremulsion for intermittent application to a spot on the animal, generallybetween the two shoulders (solution of spot-on type).

For spot-on formulations, the carrier can be a liquid carrier vehicle asdescribed in U.S. Pat. No. 6,426,333 (incorporated herein by reference),which in one embodiment of the spot-on formulation comprises a solventand a cosolvent wherein the solvent is selected from the groupconsisting of acetone, acetonitrile, benzyl alcohol, butyl diglycol,dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether,ethanol, isopropanol, methanol, ethylene glycol monoethyl ether,ethylene glycol monomethyl ether, monomethylacetamide, dipropyleneglycol monomethyl ether, liquid polyoxyethylene glycols, propyleneglycol, 2-pyrrolidone (e.g. N-methylpyrrolidone), diethylene glycolmonoethyl ether, ethylene glycol, diethyl phthalate fatty acid esters,such as the diethyl ester or diisobutyl adipate, and a mixture of atleast two of these solvents and the cosolvent is selected from the groupconsisting of absolute ethanol, isopropanol or methanol.

The liquid carrier vehicle can optionally contain a crystallizationinhibitor selected from the group consisting of an anionic surfactant, acationic surfactant, a non-ionic surfactant, an amine salt, anamphoteric surfactant or polyvinylpyrrolidone, polyvinyl alcohols,copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols,benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylenatedsorbitan esters; lecithin, sodium carboxymethylcellulose, and acrylicderivatives, or a mixture of these crystallization inhibitors.

Spot-on formulations may be prepared by dissolving the activeingredients into the pharmaceutically or veterinary acceptable vehicle.Alternatively, the spot-on formulation can be prepared by encapsulationof the active ingredient to leave a residue of the therapeutic agent onthe surface of the animal. These formulations will vary with regard tothe weight of the therapeutic agent in the combination depending on thespecies of host animal to be treated, the severity and type of infectionand the body weight of the host.

Dosage forms may contain from about 0.5 mg to about 5 g of an activeagent. In one embodiment of the dosage form, the dosage is from about 1mg to about 500 mg of an active agent, typically about 25 mg, about 50mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500mg, about 600 mg, about 800 mg, or about 1000 mg.

In one embodiment of the invention, the active agent is present in theformulation at a concentration of about 0.05 to 10% weight/volume. Inanother embodiment of the invention, the active agent is present in theformulation as a concentration from about 0.1 to 2% weight/volume. Inyet another embodiment of the invention, the active agent is present inthe formulation as a concentration from about 0.25 to about 1.5%weight/volume. In still another embodiment of the invention, the activeagent is present in the formulation as a concentration about 1%weight/volume.

Formulations and Administration for Agrochemical Use

The compounds of the formula (I) and (Ia) or their salts can be employedas such or in the form of their preparations (formulations) ascombinations with other pesticidally active substances, such as, forexample, insecticides, attractants, sterilants, acaricides, nematicides,herbicides, fungicides, and with safeners, fertilizers and/or growthregulators, for example as a premix/readymix.

The insecticides include, for example, phosphoric esters, carbamates,carboxylic esters, chlorinated hydrocarbons, phenylureas, substancesprepared by microorganisms.

Examples of insecticides which may optionally be admixed include but arenot limited to: phosphoric esters, such as azinphos-ethyl,azinphos-methyl, α-1(4-chlorophenyl)-4-(O-ethyl,S-propyl)phosphoryloxy-pyrazole, chlorpyrifos, coumaphos, demeton,demeton-S-methyl, diazinon, dichlorvos, dimethoate, ethoate,ethoprophos, etrimfos, fenitrothion, fenthion, heptenophas, parathion,parathion-methyl, phosalone, poxim, pirimiphos-ethyl, pirimiphos-methyl,profenofos, prothiofos, sulfprofos, triazophos and trichlorphon;

carbamates, such as aldicarb, bendiocarb, α-2-(1-methylpropyl)-phenylmethylcarbamate, butocarboxim, butoxycarboxim, carbaryl, carbofuran,carbosulfan, cloethocarb, isoprocarb, methomyl, oxamyl, pirimicarb,promecarb, propoxur and thiodicarb;

organosilicon compounds (e.g. dimethyl(phenyl)silyl-methyl3-phenoxybenzyl ethers, such as dimethyl-(4-ethoxyphenyl)-silylmethyl3-phenoxybenzyl ether) or (dimethylphenyl)-silyl-methyl2-phenoxy-6-pyridylmethyl ethers such as, for example,dimethyl-(9-ethoxy-phenyl)-silylmethyl 2-phenoxy-6-pyridylmethyl etheror [(phenyl)-3-(3-phenoxyphenyl)-propyl[(dimethyl)-silanes such as, forexample,(4-ethoxyphen-yl)-[3-(4-fluoro-3-phenoxyphenyl-propyl]dimethyl-silane,silafluofen;

pyrethroids (which are also useful for their repellent properties, e.g.against mosquitoes), such as allethrin, alphamethrin, bioresmethrin,byfenthrin, cycloprothrin, cyfluthirin, decamethrin, cyhalothrin,cypermethrin, deltamethrin, alpha-cyano-3-phenyl-2-methylbenzyl2,2-dimethyl-3-(2-chloro-2-trifluoro-methylvinyl)cyclopropane-carboxylate,fenpropathrin, fenfluthrin, fenvalerate, flucythrinate, flumethrin,fluvalinate, permethrin, resmethrin and tralomethrin;

nitroimines and nitromethylenes, such as1-[(6-chloro-3-pyridinyl)-methyl]-4,5-dihydro-N-nitro-1H-imidazole-2-amine(imidacloprid),N-[(6-chloro-3-pyridyl)-methyl]-N²-cyano-N¹-methylacetamide (NI-25);abamectin, AC 303, 630 (chlorfenapyr), acephate, acrinathrin, alanycarb,aldoxycarb, aldrin, amitraz, azamethiphos, Bacillus thuringiensis,phosmet, phosphamidon, phosphine, prallethrin, propaphos, propetamphos,prothoate, pyraclofos, pyrethrins, pyridaben, pyridafenthion,pyriproxyfen, quinalphos, RH-7988, rotenone, sodium fluoride, sodiumhexafluorosilicate, sulfotep, sulfuryl fluoride, tar oils,teflubenzuron, tefluthrin, temephos, terbufos, tetrachlorvinphos,tetramethrin, O-2-tert-butyl-pyrimidin-5-yl-o-isopropylphosphorothiate,thiocyclam, thiofanox, thiometon, tralomethrin, triflumuron,trimethacarb, vamidothion, Verticillium Lacanii, XMC, xylylcarb,benfuracarb, bensultap, bifenthrin, bioallethrin, MERbioallethrin(S)-cyclopentenyl isomer, bromophos, bromophos-ethyl, buprofezin,cadusafos, calcium polysulphide, carbophenothion, cartap,quinomethionate, chlordane, chlorfenvinphos, chlorfluazuron,chlormephos, chloropicrin, chlorpyrifos, cyanophos, beta-cyfluthrin,alphacypermethrin, cyophenothrin, cyromazine, dazomet, DDT,demeton-S-methylsulphone, diafenthiuron, dialifos, dicrotophos,diflubenzuron, dinoseb, deoxabenzofos, diazacarb, disulfoton, DNOC,empenthrin, endosulfan, EPN, esfenvalerate, ethiofencarb, ethion,etofenprox, fenobucarb, fenoxycarb, fensulfothion, fipronil,flucycloxuron, flufenprox, flufenoxuron, fonofos, formetanate,formothion, fosmethilan, furathiocarb, heptachlor, hexaflumuron,hydramethylnon, hydrogen cyanide, hydroprene, IPSP, isazofos,isofenphos, isoprothiolane, isoxathion, iodfenphos, kadethrin, lindane,malathion, mecarbam, mephosfolan, mercurous chloride, metam,metarthizium, anisopliae, methacrifos, methamidophos, methidathion,methiocarb, methoprene, methoxychlor, methyl isothiocyanate, metholcarb,mevinphos, monocrotophos, naled, Neodiprion sertifer NPV, nicotine,omethoate, oxydemeton-methyl, pentachlorophenol, petroleum oils,phenothrin, phenthoate, phorate.

Other insecticides that may optionally be admixed may also be from theclass of the compounds described by U.S. Pat. No. 7,001,903.

Fungicides which may optionally be admixed are include but are notlimited to:

(1) Triazoles which include but are not limited to: azaconazole,propiconazole, tebuconazole, cyproconazole, metconazole, amitrole,azocyclotin, BAS 480F, bitertanol, difenoconazole, fenbuconazole,fenchlorazole, fenethanil, fluquinconazole, flusilazole, flutriafol,imibenconazole, isozofos, myclobutanil, paclobutrazol,(±)-cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)-cycloheptanol,tetraconazole, triadimefon, triadimenol, triapenthenol, triflumizole,triticonazole, uniconazole and their metal salts and acid adducts.(2) Imidazoles which include but are not limited to: imazalil,pefurazoate, prochloraz, triflumizole,2-(1-tert-butyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol,thiazolecarboxanilides such as2′,6′-dibromo-2-methyl-4-trifluoromethoxy-4′-trifluoromethyl-1,3-thiazole-5-carboxanilide,1-imidazolyl-1-(4′-chlorophenoxy)-3,3-dimethylbutan-2-one and theirmetal salts and acid adducts.(3) “Methyl (E)-2-phenyl-3-methoxyacrylate” compounds which include butare not limited to:

-   methyl    (E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]3-methoxyacrylate,-   methyl    (E)-2-[2-[6-(2-thioamidophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[6-(2-fluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[6-(2,6-difluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[3-(pyrimidin-2-yloxy)phenoxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[3-(5-methylpyrimidin-2-yloxy)-phenoxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[3-(phenyl-sulphonyloxy)phenoxy]phenyl-3-methoxyacrylate,-   methyl    (E)-2-[2-[3-(4-nitrophenoxy)phenoxy]phenyl]-3-methoxyacrylate,-   methyl (E)-2-[2-phenoxyphenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-(3,5-dimethyl-benzoyl)pyrrol-1-yl]-3-methoxyacrylate,-   methyl (E)-2-[2-(3-methoxyphenoxy)phenyl]-3-methoxyacrylate,-   methyl (E)-2[2-(2-phenylethen-1-yl)-phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-(3,5-dichlorophenoxy)pyridin-3-yl]-3-methoxyacrylate,-   methyl    (E)-2-(2-(3-(1,1,2,2-tetrafluoroethoxy)phenoxy)phenyl)-3-methoxyacrylate,-   methyl    (E)-2-(2-[3-(alpha-hydroxybenzyl)phenoxy]phenyl)-3-methoxyacrylate,-   methyl (E)-2-(2-(4-phenoxypyridin-2-yloxy)phenyl)-3-methoxyacrylate,-   methyl (E)-2-[2-(3-n-propyloxyphenoxy)phenyl]3-methoxyacrylate,-   methyl (E)-2-[2-(3-isopropyloxyphenoxy)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[3-(2-fluorophenoxy)phenoxy]phenyl]-3-methoxyacrylate,-   methyl (E)-2-[2-(3-ethoxyphenoxy)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-(4-tert-butyl-pyridin-2-yloxy)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[3-(3-cyanophenoxy)phenoxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[(3-methylpyridin-2-yloxymethyl)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[6-(2-methylphenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-(5-bromo-pyridin-2-yloxymethyl)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-(3-(3-iodopyridin-2-yloxy)phenoxy)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-[2-[6-(2-chloropyridin-3-yloxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate,    methyl    (E),(E)-2-[2-(5,6-di-methylpyrazin-2-ylmethyloximinomethyl)phenyl]-3-methoxyacrylate,-   methyl    (E)-2-{2-[6-(6-methylpyridin-2-yloxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate,    methyl    (E),(E)-2-{2-(3-methoxyphenyl)methyloximinomethyl]-phenyl}-3-methoxyacrylate,    methyl    (E)-2-{2-(6-(2-azidophenoxy)-pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate,-   methyl    (E),(E)-2-{2-[6-phenylpyrimidin-4-yl)-methyloximinomethyl]phenyl}-3-methoxyacrylate,-   methyl    (E),(E)-2-{2-[(4-chlorophenyl)-methyloximinomethyl]-phenyl}-3-methoxyacrylate,    methyl    (E)-2-{2-[6-(2-n-propylphenoxy)-1,3,5-triazin-4-yloxy]phenyl}-3-methoxyacrylate,    and methyl    (E),(E)-2-{2-[(3-nitrophenyl)methyloximinomethyl]phenyl}-3-methoxyacrylate;    (4) Succinate Dehydrogenase Inhibitors which include but are not    limited to:    -   (a) fenfuram, furcarbanil, cyclafluramid, furmecyclox, seedvax,        metsulfovax, pyrocarbolid, oxycarboxin, shirlan, mebenil        (mepronil), benodanil, flutolanil (Moncut);    -   (b) naphthalene derivatives such as terbinafine, naftifine,        butenafine, 3-chloro-7-(2-aza-2,7,7-trimethyl-oct-3-en-5-ine);    -   (c) sulphenamides such as dichlofluanid, tolylfluanid, folpet,        fluorfolpet; captan, captofol;    -   (d) benzimidazoles such as carbendazim, benomyl, furathiocarb,        fuberidazole, thiophonatmethyl, thiabendazole or their salts;    -   (e) morpholine derivatives such as fenpropimorph, falimorph,        dimethomorph, dodemorph, aldimorph, fenpropidine and their        arylsulphonates, such as, for example, p-toluenesulphonic acid        and p-dodecylphenyl-sulphonic acid;    -   (f) dithiocarbamates, cufraneb, ferbam, mancopper, mancozeb,        maneb, metam, metiram, thiram zeneb, ziram;    -   (g) benzothiazoles, such as 2-mercaptobenzothiazole;    -   (h) benzamides, such as        2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide;    -   (i) boron compounds, such as boric acid, boric esters, borax;    -   (j) formaldehyde and formaldehyde-releasing compounds, such as        benzyl alcohol mono-(poly)-hemiformal, oxazolidine,        hexa-hydro-S-triazines, N-methylolchloroacetamide,        paraformaldehyde, nitropyrin, oxolinic acid, tecloftalam;    -   (k) tris-N-(cyclohexyldiazeniumdioxy)-aluminium,        N-(cyclo-hexyldiazeniumdioxy)-tri-butyltin or K salts,        bis-N-(cyclohexyldiazeniumdioxy)-copper,        N-methylisothiazolin-3-one, 5-chloro-N-methylisothiazolin-3-one,        4,5-dichloro-N-octylisothiazolin-3-one,        N-octyl-isothiazolin-3-one, 4,5-trimethylene-isothiazolinone,        4,5-benzoisothiazolinone, N-methylolchloroacetamide;    -   (l) aldehydes, such as cinnamaldehyde, formaldehyde,        glutaraldehyde, 6-bromo-cinnamaldehyde;    -   (m) thiocyanates, such as thiocyanatomethylthiobenzothiazole,        methylenebisthiocyanate, and the like;    -   (n) quaternary ammonium compounds, such as        benzyldimethyltetradecylammonium chloride,        benzyldimethyldodecylanmuonium chloride, didecyldimethylammonium        chloride;    -   (o) iodine derivatives, such as diiodomethyl p-tolyl sulphone,        3-iodo-2-propinyl alcohol, 4-chlorophenyl-3-iodopropargyl        formal, 3-bromo-2,3-diiodo-2-propenyl ethylcarbamate,        2,3,3-triiodoallyl alcohol, 3-bromo-2,3-diiodo-2-propenyl        alcohol, 3-iodo-2-propinyl n-butylcarbamate, 3-iodo-2-propinyl        n-hexylcarbamate, 3-iodo-2-propinyl cyclohexyl-carbamate,        3-iodo-2-propinyl phenylcarbamate;    -   (p) phenol derivatives, such as tribromophenol,        tetrachlorophenol, 3-methyl-4-chlorophenol,        3,5-dimethyl-4-chlorophenol, phenoxyethanol, dichlorophene,        o-phenylphenol, m-phenylphenol, p-phenylphenol,        2-benzyl-4-chlorophenol and their alkali metal and alkaline        earth metal salts;    -   (q) microbicides having an activated halogen group, such as        chloroacetamide, bronopol, bronidox, tectamer, such as        2-bromo-2-nitro-1,3-propanediol, 2-bromo-4′-hydroxyacetophenone,        2,2-dibromo-3-nitrile-propionamide,        1,2-dibromo-2,4-dicyanobutane, β-bromo-β-nitrostyrene;    -   (r) pyridines, such as 1-hydroxy-2-pyridinethione (and their Na,        Fe, Mn, Zn salts), tetrachloro-4-methylsulphonylpyridine,        pyrimethanol, mepanipyrim, dipyrithion,        1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridine;    -   (s) metal soaps, such as tin naphthenate, copper naphthenate,        zinc naphthenate, tin octoate, copper octoate, zinc octoate, tin        2-ethylhexanoate, copper 2-ethylhexanoate, zinc        2-ethylhexanoate, tin oleate, copper oleate, zinc oleate, tin        phosphate, copper phosphate, zinc phosphate, tin benzoate,        copper benzoate and zinc benzoate;    -   (t) metal salts, such as copper hydroxycarbonate, sodium        dichromate, potassium dichromate, potassium chromate, copper        sulphate, copper chloride, copper borate, zinc fluorosilicate,        copper fluorosilicate, and mixtures with fixatives;    -   (u) oxides, such as tributyltin oxide, Cu₂O, CuO, ZnO;    -   (v) dialkyldithiocarbamates, such as Na and Zn salts of        dialkyldithiocarbamates, tetramethylthiuram disulphide,        potassium N-methyl-dithiocarbamate;    -   (w) nitriles, such as 2,4,5,6-tetrachloroisophthalodinitrile,        disodium cyano-dithioimido-carbamate;    -   (x) quinolines, such as 8-hydroxyquinoline, and their Cu salts;    -   (y) mucochloric acid, 5-hydroxy-2(5H)-furanone;    -   (z) 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone,        4,5-trimethylenedithiazolinone,        4,5-dichloro-(3H)-1,2-dithiol-3-one,        3,5-dimethyl-tetrahydro-1,3,5-thiadiazine-2-thione,        N-(2-p-chlorobenzoylethyl)-hexaminium chloride, potassium        N-hydroxymethyl-N′-methyl-dithiocarbamate,        2-oxo-2-(4-hydroxy-phenyl)acetohydroximic acid chloride,        phenyl-(2-chloro-cyano-vinyl)sulphone,        phenyl-(1,2-dichloro-2-cyano-vinyl)sulphone; and    -   (aa) Ag-, Zn- or Cu-containing zeolites, alone or enclosed in        polymeric active compounds, or    -   (bb) mixtures of more than one of the abovementioned fungicides.

Herbicides which are known from the literature and which can bementioned, which can be combined with the compounds of the formula (I)and (Ia), are, for example, the following active substances (Note: thecompounds are either designated by the common name according to theInternational Organization for Standardization (ISO) or using thechemical name, if appropriate together with a customary code number):acetochlor; acifluorfen(-sodium); aclonifen; AKH 7088, i.e.[[[1-[5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrophenyl]-2-methoxyethylidene]amino]oxy]aceticacid and its methyl ester; alachlor; alloxydim(-sodium); ametryn;amicarbazone, amidochlor, amidosulfuron; amitrol; AMS, i.e. ammoniumsulfamate; anilofos; asulam; atrazine; azafenidin; azimsulfuron(DPX-A8947); aziprotryn; barban; BAS 516H, i.e.5-fluoro-2-phenyl-4H-3,1-benzoxazin-4-one; beflubutamid;benazolin(-ethyl); benfluralin; benfuresate; bensulfuron(-methyl);bensulide; bentazone(-sodium); benzobicyclone; benzofenap; benzofluor;benzoylprop(-ethyl); benzthiazuron; bialaphos (bilanafos); bifenox;bispyribac(-sodium); bromacil; bromobutide; bromofenoxim; bromoxynil;bromuron; buminafos; busoxinone; butachlor; butafenacil; butamifos;butenachlor; buthidazole; butralin; butroxydim; butylate; cafenstrole(CH-900); carbetamide; carfentrazone(-ethyl); caloxydim, CDAA, i.e.2-chloro-N,N-di-2-propenylacetamide; CDEC, i.e. 2-chloroallyldiethyldithiocarbamate; chlomethoxyfen; chloramben; chlorazifop-butyl;chlorbromuron; chlorbufam; chlorfenac; chlorflurenol-methyl;chloridazon; chlorimuron(-ethyl); chlornitrofen; chlorotoluron;chloroxuron; chlorpropham; chlorsulfuron; chlorthal-dimethyl;chlorthiamid; chlortoluron, cinidon(-methyl or -ethyl), cinmethylin;cinosulfuron; clethodim; clefoxydim, clodinafop and its esterderivatives (for example clodinafop-propargyl); clomazone; clomeprop;cloproxydim; clopyralid; clopyrasulfuron(-methyl); cloransulam(-methyl);cumyluron (JC 940); cyanazine; cycloate; cyclosulfamuron (AC 104);cycloxydim; cycluron; cyhalofop and its ester derivatives (for examplebutyl-ester, DEH-112); cyperquat; cyprazine; cyprazole; daimuron; 2,4-D;2,4-DB; dalapon; dazomet, desmedipham; desmetryn; di-allate; dicamba;dichlobenil; dichlorprop(-P); diclofop and its esters such asdiclofop-methyl; diclosulam, diethatyl(-ethyl); difenoxuron;difenzoquat; diflufenican; diflufenzopyr; dimefuron; dimepiperate;dimethachlor; dimethametryn; dimethenamid (SAN-582H); dimethenamid(-P);dimethazone, dimethipin; dimexyflam, dimetrasulfuron, dinitramine;dinoseb; dinoterb; diphenamid; dipropetryn; diquat; dithiopyr; diuron;DNOC; eglinazine-ethyl; EL 77, i.e.5-cyano-1-(1,1-dimethylethyl)-N-methyl-1H-pyrazole-4-carboxamide;endothal; epoprodan, EPTC; esprocarb; ethalfluralin;ethametsulfuron-methyl; ethidimuron; ethiozin; ethofumesate; ethoxyfenand its esters (for example ethyl ester, HC-252), ethoxysulfuron,etobenzanid (HW 52); F5231, i.e.N-[2-chloro-4-fluoro-5-[4-(3-fluoropropyl)-4,5-dihydro-5-oxo-1H-tetrazol-1-yl]-phenyl]ethanesulfonamide;fenoprop; fenoxan, fenoxapropand fenoxaprop-P and their esters, forexample fenoxaprop-P-ethyl and fenoxaprop-ethyl; fenoxydim;fentrazamide; fenuron; flamprop(-methyl or -isopropyl or -isopropyl-L);flazasulfuron; florasulam; fluazifop and fluazifop-P and their esters,for example fluazifop-butyl and fluazifop-P-butyl; fluazolate,flucarbazone(-sodium); fluchloralin; flufenacet (FOE 5043), flufenpyr,flumetsulam; flumeturon; flumiclorac(-pentyl); flumioxazin (S-482);flumipropyn; fluometuron; fluorochloridone, fluorodifen;fluoroglycofen(-ethyl); flupoxam (KNW-739); flupropacil (UBIC-4243);fluproanate, flupyrsulfuron(-methyl, or -sodium); flurenol(-butyl);fluridone; fluorochloridone; fluoroxypyr(-meptyl); flurprimidol,flurtamone; fluthiacet(-methyl); fluthiamide (also known as flufenacet);fomesafen; foramsulfuron; fosamine; furilazole (MON 13900), furyloxyfen;glufosinate(-ammonium); glyphosate(-isopropylammonium); halosafen;halosulfuron(-methyl) and its esters (for example the methyl ester,NC-319); haloxyfop and its esters; haloxyfop-P (=R-haloxyfop) and itsesters; HC-252 (diphenylether), hexazinone; imazamethabenz(-methyl);imazamethapyr; imazamox; imazapic, imazapyr; imazaquin and salts such asthe ammonium salts; imazethamethapyr; imazethapyr, imazosulfuron;indanofan; iodosulfuron-(methyl)-(sodium), ioxynil; isocarbamid;isopropalin; isoproturon; isouron; isoxaben; isoxachlortole;isoxaflutole; isoxapyrifop; karbutilate; lactofen; lenacil; linuron;MCPA; MCPB; mecoprop; mefenacet; mefluidid; mesosulfuron(-methyl);mesotrione; metam, metamifop, metamitron; metazachlor;methabenzthiazuron; methazole; methoxyphenone; methyldymron;metobenzuron, metobromuron; (S-)metolachlor; metosulam (XRD 511);metoxuron; metribuzin; metsulfuron-methyl; MK-616; molinate; monalide;monocarbamide dihydrogensulfate; monolinuron; monuron; MT 128, i.e.6-chloro-N-(3-chloro-2-propenyl)-5-methyl-N-phenyl-3-pyridazinamine; MT5950, i.e. N-[3-chloro-4-(1-methylethyl)-phenyl]-2-methylpentanamide;naproanilide; napropamide; naptalam; NC 310, i.e.4-(2,4-dichlorobenzoyl)-1-methyl-5-benzyloxypyrazole; neburon;nicosulfuron; nipyraclophen; nitralin; nitrofen; nitrofluorfen;norflurazon; orbencarb; oryzalin; oxadiargyl (RP-020630); oxadiazone;oxasulfuron; oxaziclomefone; oxyfluorfen; paraquat; pebulate; pelargonicacid; pendimethalin; penoxulam; pentanochlor, pentoxazone; perfluidone;pethoxamid, phenisopham; phenmedipham; picloram; picolinafen;piperophos; piributicarb; pirifenop-butyl; pretilachlor;primisulfuron(-methyl); procarbazone(-sodium); procyazine; prodiamine;profluazole, profluralin; proglinazine(-ethyl); prometon; prometryn;propachlor; propanil; propaquizafop; propazine; propham; propisochlor;propoxycarbazone(-sodium), propyzamide; prosulfalin; prosulfocarb;prosulfuron (CGA-152005); prynachlor; pyraclonil, pyraflufen(-ethyl);pyrazolinate; pyrazon; pyrazosulfuron(-ethyl); pyrazoxyfen;pyribenzoxim; pyributicarb; pyridafol; pyridate; pyriftalid,pyrimidobac(-methyl); pyrithiobac(-sodium) (KIH-2031); pyroxofop and itsesters (for example propargyl ester); quinclorac; quinmerac;quinoclamine, quinofop and its ester derivatives, quizalofop andquizalofop-P and their ester derivatives, for example quizalofop-ethyl;quizalofop-P-tefuryl and -ethyl; renriduron; rimsulfuron (DPX-E 9636); S275, i.e.2-[4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]-4,5,6,7-tetrahydro-2H-indazole;secbumeton; sethoxydim; siduron; simazine; simetryn; SN 106279, i.e.2-[[7-[2-chloro-4-(trifluoromethyl)phenoxy]-2-naphthalenyl]oxy]propanoicacid and its methyl ester; sulcotrione; sulfentrazone (FMC-97285,F-6285); sulfazuron; sulfometuron(-methyl); sulfosate (ICI-A0224);sulfosulfuron; TCA; tebutam (GCP-5544); tebuthiuron; tepraloxydim;terbacil; terbucarb; terbuchlor; terbumeton; terbuthylazine; terbutryn;TFH 450, i.e.N,N-diethyl-3-[(2-ethyl-6-methylphenyl)sulfonyl]-1H-1,2,4-triazole-1-carboxamide;thenylchlor (NSK-850); thiafluamide; thiazafluoron; thiazopyr(Mon-13200); thidiazimin (SN-24085); thifensulfuron(-methyl);thiobencarb; tiocarbazil; tralkoxydim; tri-allate; triasulfuron;triaziflam; triazofenamide; tribenuron(-methyl); 2,3,6-trichlorobenzoicacid (2,3,6-TBA), triclopyr; tridiphane; trietazine;trifloxysulfuron(-sodium), trifluralin; triflusulfuron and esters (e.g.methyl ester, DPX-66037); trimeturon; tritosulfuron; tsitodef;vernolate; WL 110547, i.e.5-phenoxy-1-[3-(trifluoromethyl)phenyl]-1H-tetrazole; UBH-509; D-489; LS82-556; KPP-300; NC-324; NC-330; KH-218; DPX-N8189; SC-0774; DOWCO-535;DK-8910; V-53482; PP-600; MBH-001; KIH-9201; ET-751; KIH-6127; KIH-2023and KIH5996.

Appropriate herbicide safeners include but are not limited to benoxacor,cloquintocet, cyometrinil, cyprosulfamide, dichlormid, dicyclonon,dietholate, fenchlorazole, fenclorim, flurazole, fluxofenim, furilazole,isoxadifen, mefenpyr, mephenate, naphthalic anyhydride and oxabetrinil.

Components which may be employed for the active substances according tothe invention in mixed formulations, for example, known active compoundswhich are based on an inhibition of, for example, acetolactate synthase,acetyl-coenzyme A carboxylase, PS I, PS II, HPPDO, phytoene desaturase,protoporphyrinogen oxidase, glutamine synthetase, cellulosebiosynthesis, 5-enolpyruvylshikimate-3-phosphate synthetase. Suchcompounds, and also other compounds which can be employed, whosemechanism of action is to a degree unknown or different, are described,for example, in Weed Research 26, 441-445 (1986), or “The PesticideManual”, 12th Edition 2000 (hereinbelow also abbreviated to “PM”), TheBritish Crop Protection Council and the Royal Soc. of Chemistry(editors) and literature cited therein.

The compounds of formula (I) and formula (Ia) can be formulated invarious ways, depending on the prevailing biological and/orchemico-physical parameters. Examples of possible formulations which aresuitable are: wettable powders (WP), water-soluble powders (SP),water-soluble concentrates, emulsifiable concentrates (EC), emulsions(EW) such as oil-in-water and water-in-oil emulsions, sprayablesolutions, suspension concentrates (SC), dispersions on an oil or waterbasis, solutions which are miscible with oil, capsule suspensions (CS),dusts (DP), seed-dressing products, granules for broadcasting and soilapplication, granules (GR) in the form of microgranules, spray granules,coated granules and adsorption granules, water-dispersible granules(WG), water-soluble granules (SG), ULV formulations, microcapsules andwaxes.

The formulations mentioned can be prepared in a manner known per se, forexample by mixing the active compounds with at least one solvent ordiluent, emulsifier, dispersant and/or binder or fixative, waterrepellent and optionally one or more of a desiccant, UV stabilizer, acolorant, a pigment and other processing auxiliaries.

These individual formulation types are known in principle and described,for example, in: Winnacker-Küchler, “Chemische Technologie” [ChemicalTechnology], Volume 7, C. Hauser Verlag, Munich, 4th Edition 1986; Wadevan Valkenburg, “Pesticide Formulations”, Marcel Dekker, N.Y., 1973; K.Martens, “Spray Drying Handbook”, 3rd Ed. 1979, G. Goodwin Ltd. London.

The necessary formulation auxiliaries such as inert materials,surfactants, solvents and other additives are also known and described,for example, in: Watkins, “Handbook of Insecticide Dust Diluents andCarriers”, 2nd Ed., Darland Books, Caldwell N. J.; H.v. Olphen,“Introduction to Clay Colloid Chemistry”, 2nd Ed., J. Wiley & Sons,N.Y.; C. Marsden, “Solvents Guide”, 2nd Ed., Interscience, N.Y. 1963;McCutcheon's “Detergents and Emulsifiers Annual”, MC Publ. Corp.,Ridgewood N.J.; Sisley and Wood, “Encyclopedia of Surface ActiveAgents”, Chem. Publ. Co. Inc., N.Y. 1964; Schönfeldt,“Grenzflächenaktive Äthylenoxidaddukte” [Surface-active ethylene oxideadducts], Wiss. Verlagsgesell., Stuttgart 1976; Winnacker-Küchler,“Chemische Technologie” [Chemical Technology], Volume 7, C. HauserVerlag, Munich, 4th Ed. 1986.

Wettable powders are preparations which are uniformly dispersible inwater and which, besides the compounds of formula (I) and formula (Ia),also comprise ionic and/or nonionic surfactants (wetters, dispersants),for example, polyoxyethylated alkylphenols, polyoxyethylated fattyalcohols, polyoxyethylated fatty amines, fatty alcohol polyglycol ethersulfates, alkanesulfonates or alkylbenzenesulfonates, sodiumlignosulfonate, sodium 2,2′-dinaphthylmethane-6,6′-disulfonate, sodiumdibutylnaphthalenesulfonate or else sodium oleoylmethyltaurinate, inaddition to a diluent or inert substance. To prepare the wettablepowders, the compounds of formula (I) and (Ia) are, for example, groundfinely in conventional apparatuses such as hammer mills, blower millsand air-jet mills and mixed with the formulation auxiliaries, eitherconcomitantly or thereafter.

Emulsifiable concentrates are prepared, for example, by dissolving thecompounds of formula (I) and formula (Ia) in an organic solvent, forexample butanol, cyclohexanone, dimethylformamide, xylene or elsehigher-boiling aromatics or hydrocarbons or mixtures of these, withaddition of one or more ionic and/or nonionic surfactants (emulsifiers).Emulsifiers which can be used are, for example: calcium salts ofalkylarylsulfonic acids, such as calcium dodecylbenzenesulfonate ornonionic emulsifiers, such as fatty acid polyglycol esters, alkylarylpolyglycol ethers, fatty alcohol polyglycol ethers, propyleneoxide/ethylene oxide condensates, alkyl polyethers, sorbitan esters suchas sorbitan fatty acid esters or polyoxyethylene sorbitan esters such aspolyoxyethylene sorbitan fatty acid esters.

Dusts are obtained by grinding the active substance with finely dividedsolid substances, for example talc or natural clays, such as kaolin,bentonite or pyrophyllite, or diatomaceous earth.

Suspension concentrates may be water- or oil-based. They can beprepared, for example, by wet grinding by means of commerciallyavailable bead mills, if appropriate with addition of surfactants, asthey have already been mentioned above for example in the case of theother formulation types.

Emulsions, for example oil-in-water emulsions (EW), can be prepared forexample by means of stirrers, colloid mills and/or static mixtures usingaqueous organic solvents and, if appropriate, surfactants as they havealready been mentioned above for example in the case of the otherformulation types.

Granules can be prepared either by spraying the compounds of formula (I)and formula (Ia) onto adsorptive, granulated inert material or byapplying active substance concentrates onto the surface of carriers suchas sand, kaolinites or of granulated inert material, by means ofbinders, for example polyvinyl alcohol, sodium polyacrylate oralternatively mineral oils. Suitable active substances can also begranulated in the manner which is conventional for the production offertilizer granules, if desired in a mixture with fertilizers.

Water-dispersible granules are prepared, as a rule, by the customaryprocesses such as spray-drying, fluidized-bed granulation, diskgranulation, mixing in high-speed mixers and extrusion without solidinert material. To prepare disk, fluidized-bed, extruder and spraygranules, see, for example, processes in “Spray-Drying Handbook” 3rd ed.1979, G. Goodwin Ltd., London; J. E. Browning, “Agglomeration”, Chemicaland Engineering 1967, pages 147 et seq.; “Perry's Chemical EngineersHandbook”, 5th Ed., McGraw-Hill, New York 1973, p. 8-57.

In general, the agrochemical preparations comprise a range selected fromthe group consisting of about 0.1 to about 99% by weight and about 0.1to about 95% by weight, of compounds of formula (I) and (Ia).

The concentration of compounds of formula (I) and (Ia) in wettablepowders is, for example, about 10 to about 90% by weight, the remainderto 100% by weight being composed of customary formulation components. Inthe case of emulsifiable concentrates, the concentration of compounds offormula (I) and formula (Ia) can amount to ranges selected from thegroup consisting of about 1% to about 90% and about 5% to about 80% byweight. Formulations in the form of dusts usually comprise in the rangeselected from the group consisting of about 1% to about 30% by weight ofcompounds of formula (I) and formula (Ia) and about 5% to about 20% byweight of compounds of formula (I). For sprayable solutions comprise arange selected from the group consisting of about 0.05% to about 80% byweight of compounds of formula (I) and formula (Ia) and about 2% toabout 50% by weight of compounds of formula (I) and formula (Ia). In thecase of water-dispersible granules, the content of compounds of formula(I) and formula (Ia) depends partly on whether the compounds of formula(I) and formula (Ia) are in liquid or solid form and on whichgranulation auxiliaries, fillers and the like are being used. Thewater-dispersible granules, for example, comprise a range selected fromthe group consisting of between about 1 and about 95% and between about10% and about 80% by weight.

In addition, the formulations of compounds of formula (I) and formula(Ia) mentioned comprise, if appropriate, the adhesives, wetters,dispersants, emulsifiers, penetrants, preservatives, antifreeze agents,solvents, fillers, carriers, colorants, antifoams, evaporationinhibitors, pH regulators and viscosity regulators which areconventional in each case.

The mixtures according to the invention can be applied via the soileither pre-emergently or post-emergently. The mixtures according to theinvention can also be applied via the leaf. The mixtures according tothe invention can be employed for seed dressing. It is also possible toapply the mixtures according to the invention via an irrigation system,for example via the water for irrigation.

Other Active Agents for Pharmaceutical/Veterinary Use

Additional pesticidally or veterinarily active ingredients, whichinclude, but are not limited to, acaricides, anthelmintics,anti-parasitics and insecticides, may also be added to the compositionsof the invention in combination with compounds of formula (I) or (Ia).Anti-parasitic agents can include both ectoparasiticisal andendoparasiticidal agents. These agents are well-known in the art (seee.g. Plumb' Veterinary Drug Handbook, 5^(th) Edition, ed. Donald C.Plumb, Blackwell Publishing, (2005) or The Merck Veterinary Manual,9^(th) Edition, (January 2005)) and include but are not limited toacarbose, acepromazine maleate, acetaminophen, acetazolamide,acetazolamide sodium, acetic acid, acetohydroxamic acid, acetylcysteine,acitretin, acyclovir, albendazole, albuterol sulfate, alfentanil HCl,allopurinol, alprazolam, altrenogest, amantadine HCl, amikacin sulfate,aminocaproic acid, aminopentamide hydrogen sulfate,aminophylline/theophylline, amiodarone HCl, amitraz, amitriptyline HCl,amlodipine besylate, ammonium chloride, ammonium molybdenate,amoxicillin, amoxicillin, clavulanate potassium, amphotericin Bdesoxycholate, amphotericin B lipid-based, ampicillin, amprolium HCl,antacids (oral), antivenin, apomorphione HCl, apramycin sulfate,ascorbic acid, asparaginase, aspiring, atenolol, atipamezole HCl,atracurium besylate, atropine sulfate, aurnofin, aurothioglucose,azaperone, azathioprine, azithromycin, baclofen, barbituates, benazeprilHCl, betamethasone, bethanechol chloride, bisacodyl, bismuthsubsalicylate, bleomycin sulfate, boldenone undecylenate, bromides,bromocriptine mesylate, budenoside, buprenorphine HCl, buspirone HCl,busulfan, butorphanol tartrate, cabergoline, calcitonin salmon,calcitrol, calcium salts, captopril, carbenicillin indanyl sodium,carbimazole, carboplatin, carnitine, carprofen, carvedilol, cefadroxil,cefazolin sodium, cefixime, cefoperazone sodium, cefotaxime sodium,cefotetan disodium, cefoxitin sodium, cefpodoxime proxetil, ceftazidime,ceftiofur sodium, ceftiofur HCl, ceftiaxone sodium, cephalexin,cephalosporins, cephapirin, charcoal (activated), chlorambucil,chloramphenicol, chlordiazepoxide, chlordiazepoxide+/−clidinium bromide,chlorothiazide, chlorpheniramine maleate, chlorpromazine HCl,chlorpropamide, chlortetracycline, chorionic gonadotropin (HCG),chromium, cimetidine, ciprofloxacin, cisapride, cisplatin, citratesalts, clarithromycin, clemastine fumarate, clenbuterol HCl,clindamycin, clofazimine, clomipramine HCl, claonazepam, clonidine,cloprostenol sodium, clorazepate dipotassium, clorsulon, cloxacillin,codeine phosphate, colchicine, corticotropin (ACTH), cosyntropin,cyclophosphamide, cyclosporine, cyproheptadine HCl, cytarabine,dacarbazine, dactinomycin/actinomycin D, dalteparin sodium, danazol,dantrolene sodium, dapsone, decoquinate, deferoxamine mesylate,deracoxib, deslorelin acetate, desmopressin acetate,desoxycorticosterone pivalate, detomidine HCl, dexamethasone,dexpanthenol, dexraazoxane, dextran, diazepam, diazoxide (oral),dichlorphenamide, dichlorvos, diclofenac sodium, dicloxacillin,diethylcarbamazine citrate, diethylstilbestrol (DES), difloxacin HCl,digoxin, dihydrotachysterol (DHT), diltiazem HCl, dimenhydrinate,dimercaprol/BAL, dimethyl sulfoxide, dinoprost tromethamine,diphenylhydramine HCl, disopyramide phosphate, dobutamine HCl,docusate/DSS, dolasetron mesylate, domperidone, dopamine HCl,doramectin, doxapram HCl, doxepin HCl, doxorubicin HCl, doxycycline,edetate calcium disodium.calcium EDTA, edrophonium chloride,enalapril/enalaprilat, enoxaparin sodium, enrofloxacin, ephedrinesulfate, epinephrine, epoetin/erythropoietin, eprinomectin, epsiprantel,erythromycin, esmolol HCl, estradiol cypionate, ethacrynicacid/ethacrynate sodium, ethanol (alcohol), etidronate sodium, etodolac,etomidate, euthanasia agents w/pentobarbital, famotidine, fatty acids(essential/omega), felbamate, fenbendazole, fentanyl, ferrous sulfate,filgrastim, finasteride, fipronil, florfenicol, fluconazole,flucytosine, fludrocortisone acetate, flumazenil, flumethasone, flunixinmeglumine, fluorouracil (5-FU), fluoxetine, fluticasone propionate,fluvoxamine maleate, fomepizole (4-MP), furazolidone, furosemide,gabapentin, gemcitabine HCL, gentamicin sulfate, glimepiride, glipizide,glucagon, glucocorticoid agents, glucosamine/chondroitin sulfate,glutamine, glyburide, glycerine (oral), glycopyrrolate, gonadorelin,grisseofulvin, guaifenesin, halothane, hemoglobin glutamer-200(Oxyglobin®), heparin, hetastarch, hyaluronate sodium, hydrazaline HCl,hydrochlorothiazide, hydrocodone bitartrate, hydrocortisone,hydromorphone, hydroxyurea, hydroxyzine, ifosfamide, imidacloprid,imidocarb dipropinate, impenem-cilastatin sodium, imipramine, inaminonelactate, insulin, interferon alfa-2a (human recombinant), iodide(sodium/potassium), ipecac (syrup), ipodate sodium, iron dextran,isoflurane, isoproterenol HCl, isotretinoin, isoxsuprine HCl,itraconazole, ivermectin, kaolin/pectin, ketamine HCl, ketoconazole,ketoprofen, ketorolac tromethamine, lactulose, leuprolide, levamisole,levetiracetam, levothyroxine sodium, lidocaine HCl, lincomycin HCl,liothyronine sodium, lisinopril, lomustine (CCNU), lufenuron, lysine,magnesium, mannitol, marbofloxacin, mechlorethamine HCl, meclizine HCl,meclofenamic acid, medetomidine HCl, medium chain triglycerides,medroxyprogesterone acetate, megestrol acetate, melarsomine, melatonin,meloxican, melphalan, meperidine HCl, mercaptopurine, meropenem,metformin HCl, methadone HCl, methazolamide, methenaminemandelate/hippurate, methimazole, methionine, methocarbamol,methohexital sodium, methotrexate, methoxyflurane, methylene blue,methylphenidate, methylprednisolone, metoclopramide HCl, metoprolol,metronidaxole, mexiletine HCl, mibolerlone, midazolam HCl milbemycinoxime, mineral oil, minocycline HCl, misoprostol, mitotane, mitoxantroneHCl, morantel tartrate, morphine sulfate, moxidectin, naloxone HCl,mandrolone decanoate, naproxen, narcotic (opiate) agonist analgesics,neomycin sulfate, neostigmine, niacinamide, nitazoxanide, nitenpyram,nitrofurantoin, nitroglycerin, nitroprusside sodium, nizatidine,novobiocin sodium, nystatin, octreotide acetate, olsalazine sodium,omeprozole, ondansetron, opiate antidiarrheals, orbifloxacin, oxacillinsodium, oxazepam, oxfendazole, oxibutynin chloride, oxymorphone HCl,oxytretracycline, oxytocin, pamidronate disodium, pancreplipase,pancuronium bromide, paromomycin sulfate, parozetine HCl, pencillamine,general information penicillins, penicillin G, penicillin V potassium,pentazocine, pentobarbital sodium, pentosan polysulfate sodium,pentoxifylline, pergolide mesylate, phenobarbital, phenoxybenzamine HCl,phenylbutazone, phenylephrine HCL, phenylpropanolamine HCl, phenyloinsodium, pheromones, parenteral phosphate, phytonadione/vitamin K-1,pimobendan, piperazine, pirlimycin HCL, piroxicam, polysulfatedglycosaminoglycan, ponazuril, potassium chloride, pralidoxime chloride,praziquantel, prazosin HCl, prednisolone/prednisone, primidone,procainamide HCl, procarbazine HCl, prochlorperazine, propanthelinebromide, propionibacterium acnes injection, propofol, propranolol HCl,protamine sulfate, pseudoephedrine HCl, psyllium hydrophilic mucilloid,pyrantel pamoate, pyridostigmine bromide, pyrilamine maleate,pyrimethamine, quinacrine HCl, quinidine, ranitidine HCl, rifampin,s-adenosyl-methionine (SAMe), saline/hyperosmotic laxative, selamectin,selegiline HCL/I-deprenyl, sertraline HCl, sevelamer HCl, sevoflurane,silymarin/milk thistle, sodium bicarbonate, sodium polystyrenesulfonate, sodium stibogluconate, sodium sulfate, sodum thiosulfate,somatotropin, sotalol HCl, spectinomycin HCl, spironolactone,stanozolol, streptokinase, streptozocin, succimer, succinylcholinechloride, sucralfate, sufentanil citrate, sulfachlorpyridazine sodium,sulfadiazine/trimethroprim, sulfamethoxazole/trimethoprim,sulfadimentoxine, sulfadimethoxine/ormetoprim, sulfasalazine, taurine,tepoxaline, terbinafline HCl, terbutaline sulfate, testosterone,tetracycline HCl, thiabendazole, thiacetarsamide sodium, thiamine HCl,thioguanine, thiopental sodium, thiotepa, thyrotropin, tiamulin,ticarcilin disodium, tiletamine HCl/zolazepam HCl, tilmocsin, tiopronin,tobramycin sulfate, tocamide HCl, tolazoline HCl, telfenamic acid,topiramate, tramadol HCl, trimcinolone acetonide, trientine HCl,trilostane, trimepraxine tartrate w/prednisolone, tripelennamine HCl,tylosin, urdosiol, valproic acid, vanadium, vancomycin HCl, vasopressin,vecuronium bromide, verapamil HCl, vinblastine sulfate, vincristinesulfate, vitamin E/selenium, warfarin sodium, xylazine HCl, yohimbineHCl, zafirlukast, zidovudine (AZT), zinc acetate/zinc sulfate,zonisamide and mixtures thereof.

In one embodiment of the invention, arylpyrazole compounds includingphenylpyrazoles such as fipronil and derivatives of fipronil, are knownin the art and are suitable for combination with the compounds of theinvention. Examples of such arylpyrazole compounds include but are notlimited to those described in U.S. Pat. Nos. 6,001,384; 6,010,710;6,083,519; 6,096,329; 6,174,540; 6,685,954 and 6,998,131, which are allincorporated herein by reference in their entirety,—each assigned toMerial, Ltd., Duluth, Ga.).

In another embodiment of the invention, nodulisporic acid and itsderivatives (a class of known acaricidal, anthelminitic, anti-parasiticand insecticidal agents) can be added to the compositions of theinvention. These compounds are used to treat or prevent infections inhumans and animals and are described, for example, in U.S. Pat. Nos.5,399,582 and 5,962,499. The composition can include one or more of theknown nodulisporic acid derivatives in the art, including allstereoisomers, such as those described in the literature cited above.

In another embodiment, anthelmintic compounds of the amino acetonitrileclass (AAD) of compounds such as monepantel (ZOLVIX) and the like may beadded to the compositions of the invention. These compounds aredescribed, for example, in WO 2004/024704; Sager et al., VeterinaryParasitology, 2009, 159, 49-54; Kaminsky et al., Nature vol. 452, 13Mar. 2008, 176-181.

The compositions of the invention may also be combined withparaherquamide compounds and derivatives of these compounds, includingderquantel (see Ostlind et al., Research in Veterinary Science, 1990,48, 260-61; and Ostlind et al., Medical and Veterinary Entomology, 1997,11, 407-408). The paraherquamide family of compounds are known class ofcompounds that include a spirodioxepino indole core with activityagainst certain parasites (see Tet. Lett. 1981, 22, 135; J. Antibiotics1990, 43, 1380, and J. Antibiotics 1991, 44, 492). In addition, thestructurally related marcfortine family of compounds, such asmarcfortines A-C, are also known and may be combined with theformulations of the invention (see J. Chem. Soc.—Chem. Comm. 1980, 601and Tet. Lett. 1981, 22, 1977). Further references to the paraherquamidederivatives can be found, for example, in WO 91/09961, WO 92/22555, WO97/03988, WO 01/076370, WO 09/004,432, U.S. Pat. No. 5,703,078 and U.S.Pat. No. 5,750,695, all of which are hereby incorporated by reference intheir entirety.

In another embodiment, the compositions of the invention may be combinedwith cyclo-depsipeptide anthelmintic compounds including emodepside (seeWillson et al., Parasitology, January 2003, 126(Pt 1):79-86).

In another embodiment of the invention, one or more macrocycliclactones, which act as an acaricide, anthelmintic agent and insecticide,can be added to the compositions of the invention. The macrolides arewell-known in the art (see e.g. Macrolides—Chemistry, pharmacology andclinical uses—edited by Bryskier et al., publ. by Arnette Blackwell,(1993)) and include but are not limited to 12-membered ring macrolides(e.g. methymycin, neomethymycin, YC-17, litorin); 14-membered ringmacrolides (e.g. erythromycin A-F, oleandomycin, sporeamicin,roxithromycin, dirithromycin, flurithromycin, clarithromycin, davercin);15-membered ring macrolides (e.g. azithromycin); 16-membered ringmacrolides (e.g. josamycin, kitasamycin, spiramycin, midecamycin,rokitamycin, miokamicin) and 17-membered ring macrolides (e.g.lankadicin).

The macrocyclic lactones also include, but are not limited to,avermectins, such as abamectin, dimadectin, doramectin, emamectin,eprinomectin, ivermectin, latidectin, lepimectin, selamectin andmilbemycins, such as milbemectin, milbemycin D, moxidectin andnemadectin. Also included are the 5-oxo and 5-oxime derivatives of saidavermectins and milbemycins. Examples of combinations of activepesticides with macrocyclic lactones include but are not limited tothose described in U.S. Pat. Nos. 6,426,333; 6,482,425; 6,962,713 and6,998,131, each of which is incorporated herein by reference—eachassigned to Merial, Ltd., Duluth, Ga.

The macrocyclic lactone compounds are known in the art and can easily beobtained commercially or through synthesis techniques known in the art.Reference is made to the widely available technical and commercialliterature. For avermectins, ivermectin and abamectin, reference may bemade, for example, to the work “Ivermectin and Abamectin”, 1989, by M.H. Fischer and H. Mrozik, William C. Campbell, published by SpringerVerlag., or Albers-Schönberg et al. (1981), “Avermectins StructureDetermination”, J. Am. Chem. Soc., 103, 4216-4221. For doramectin,“Veterinary Parasitology”, vol. 49, No. 1, July 1993, 5-15 may beconsulted. For milbemycins, reference may be made, inter alia, to DaviesH. G. et al., 1986, “Avermectins and Milbemycins”, Nat. Prod. Rep., 3,87-121, Mrozik H. et al., 1983, Synthesis of Milbemycins fromAvermectins, Tetrahedron Lett., 24, 5333-5336, U.S. Pat. No. 4,134,973and EP 0 677 054.

Macrocyclic lactones are either natural products or are semi-syntheticderivatives thereof. The structure of the avermectins and milbemycinsare closely related, e.g., by sharing a complex 16-membered macrocycliclactone ring; milbemycins lack the glycosidic moiety of the avermectins.The natural product avermectins are disclosed in U.S. Pat. No. 4,310,519to Albers-Schönberg et al., and the 22,23-dihydro avermectin compoundsare disclosed in Chabala et al., U.S. Pat. No. 4,199,569. Mention isalso made of Kitano, U.S. Pat. No. 4,468,390, Beuvry et al., U.S. Pat.No. 5,824,653, EP 0 007 812 A1, U.K. Patent Specification 1 390 336, EP0 002 916, and Ancare New Zealand Patent No. 237 086, inter alia.Naturally occurring milbemycins are described in Aoki et al., U.S. Pat.No. 3,950,360 as well as in the various references cited in “The MerckIndex” 12^(th) ed., S. Budavari, Ed., Merck & Co., Inc. WhitehouseStation, N.J. (1996). Latidectin is described in the “InternationalNonproprietary Names for Pharmaceutical Substances (INN)”, WHO DrugInformation, vol. 17, no. 4, pp. 263-286, (2003). Semisyntheticderivatives of these classes of compounds are well known in the art andare described, for example, in U.S. Pat. No. 5,077,308, U.S. Pat. No.4,859,657, U.S. Pat. No. 4,963,582, U.S. Pat. No. 4,855,317, U.S. Pat.No. 4,871,719, U.S. Pat. No. 4,874,749, U.S. Pat. No. 4,427,663, U.S.Pat. No. 4,310,519, U.S. Pat. No. 4,199,569, U.S. Pat. No. 5,055,596,U.S. Pat. No. 4,973,711, U.S. Pat. No. 4,978,677, U.S. Pat. No.4,920,148 and EP 0 667 054.

In another embodiment of the invention, the class of acaricides orinsecticides known as insect growth regulators (IGRs) can also be addedto the compositions of the invention. Compounds belonging to this groupare well known to the practitioner and represent a wide range ofdifferent chemical classes. These compounds all act by interfering withthe development or growth of the insect pests. Insect growth regulatorsare described, for example, in U.S. Pat. No. 3,748,356; U.S. Pat. No.3,818,047; U.S. Pat. No. 4,225,598; U.S. Pat. No. 4,798,837; U.S. Pat.No. 4,751,225, EP 0 179 022 or U.K. 2 140 010 as well as U.S. Pat. Nos.6,096,329 and 6,685,954 (both assigned to Merial Ltd., Duluth, Ga.), allof which are incorporated herein by reference. Examples of IGRs suitablefor use include but are not limited to methoprene, pyriproxyfen,hydroprene, cyromazine, fluazuron, lufenuron, novaluron, pyrethroids,formamidines and1-(2,6-difluorobenzoyl)-3-(2-fluoro-4-(trifluoromethyl)phenylurea.

An anthelmintic agent that can be combined with the compound of theinvention to form a composition can be a benzenedisulfonamide compound,which includes but is not limited to clorsulon; or a cestodal agent,which includes but is not limited to praziquantel, pyrantel or morantel.

An antiparasitic agent that can be combined with the compound of theinvention to form a composition can be a biologically active peptide orprotein including, but not limited to, depsipeptides, which act at theneuromuscular junction by stimulating presynaptic receptors belonging tothe secretin receptor family resulting in the paralysis and death ofparasites. In one embodiment of the depsipeptide, the depsipeptide isemodepside.

An insecticidal agent that can be combined with the compound of theinvention to form a composition can be a spinosyn (e.g. spinosad) or asubstituted pyridylmethyl derivative compound such as imidacloprid.Agents of this class are described above, and for example, in U.S. Pat.No. 4,742,060 or in EP 0 892 060, both which are incorporated herein byreference. It would be well within the skill level of the practitionerto decide which individual compound can be used in the inventiveformulation to treat a particular infection of an insect.

Where appropriate the anthelmintic, antiparasitic and insecticial agentmay also be selected from the group of compounds described above assuitable for agrochemical use. In general, the additional pesticidalagent is included in a dose of between about 0.1 μg and about 10 mg. Inone embodiment of the invention, the additional pesticidal agent isincluded in a dose of between about 1 μg and about 10 mg. In anotherembodiment of the invention, the additional pesticidal agent is includedin a dose of about 5 to about 200 μg/kg of weight of animal. In yetanother embodiment of the invention, the additional pesticidal agent isincluded in a dose between about 0.1 to about 10 mg/kg of weight ofanimal. In still another embodiment of the invention, the additionalpesticidal agent is included in a dose between about 0.5 to 50 mg/kg.

The proportions, by weight, of the benzotriazol-2-yl-acetamidonitrilecompound and the additional pesticidal agent are for example betweenabout 5/1 and about 10,000/1. However, one of ordinary skill in the artwould be able to select the appropriate ratio ofbenzotriazol-2-yl-acetamidonitrile compound and the additionalpesticidal agent for the intended host and use thereof.

Another aspect of the invention is the process of making thearylazol-2-yl-cyanoethylamide compounds of the invention.

Method of Synthesizing the Compounds of the Invention

The compounds of formula (I) and (Ia) may be prepared by the applicationor adaptation of known methods to form thioamides (i.e. methodsheretofore used or described in the chemical literature). A summary ofsuch methods is found on the first page of the publication describingthe conversion of nitriles to thioamides with ammonium sulfide inmethanol with microwave irradiation “Simple Microwave-Assisted Methodfor the Synthesis of Primary Thioamides from Nitriles”, M. C. Bagley, K.Chapaneri, C. Glover, E. A. Merritt, Synlett, 2004, 14, 2615-2617.

For example, compounds of formula (I) are obtainable by a processwherein compound of formula (II) is reacted with ammonium sulfide orsodium hydrosulfide wherein R₃, R₄, R₅, R₆, R₇, P, Q, V, W, X, Y, Z, a,are as defined above for the compounds of formula (I).

Similarly, compounds of formula (Ia) are obtainable by a process whereincompound of formula (IIa) is reacted with ammonium sulfide wherein R₃,R₄, R₅, R₆, R₇, P, Q, V, W, X, Y, Z, a, are as defined above for thecompounds of formula (Ia)

The reaction is generally carried out in a solvent with or without thepresence of base.

The solvent to be used in the reaction includes, for example but notlimited to, water, alcoholic solvent such as methanol, ethanol and thelike, and a combination of water and such alcoholic solvent.

The base that can be used in this reaction includes, for example but notlimited to, organic bases such as triethylamine, diisopropylamine,pyridine and the like. The reaction temperature is usually in the rangeof −50° C. to 200° C., preferably in the range of −20° C. to 130° C. andthe reaction time is usually in the range of 0.1 to 72 hours.

The reaction can be carried out under pressure with or without microwaveirradiation.

After completion of the reaction, the compounds of formula (I) and (Ia)can be isolated by employing conventional methods such as adding thereaction mixture to water, extracting with an organic solvent,concentrating the extract and the like. The isolated compound of formula(I) and (Ia) can be purified by a technique such as chromatography,recrystallization and the like, if necessary. Compound of formula (II)are described in U.S. Provisional Application SN: 60/930,485 and thecompound of formula (IIa) are described in WO 2002/049641, WO2003/097036, WO 2003/097585, WO 2003/104187, WO 2004/000793, WO2005/044784, WO 2005/05802, WO 2005/121075 and WO 2006/043654 as well asin EP 953565 (U.S. Pat. No. 6,239,077) and EP 1445251.

Method of Treatment with Compounds of the Invention

Another aspect of the invention is a method for preventing or treatingan endoparasitic infestation/infection (e.g. filariae or worms) in ananimal (e.g. a mammal or bird), comprising administering anendoparasiticidally effective amount of a compound or a composition ofthe invention. Mammals which can be treated include but are not limitedto humans, cats, dogs, cattle, chickens, cows, deer, goats, horses,llamas, pigs, sheep and yaks. In one embodiment of the invention, themammals treated are humans, cats or dogs.

The endoparasites treated include but are not limited to those helminthsselected from the group consisting of Anaplocepheda, Ancylostoma,Anecator, Ascaris, Caenorhabditis, Capillaria, Cooperia, Dipyllidinum,Dirofilaria, Echinococcus, Enterobius, Fasciola, Haemonchus,Oesophagostumum, Ostertagia, Toxocara, Strongyloides, Toxascaris,Trichinella, Trichuris, Trichostrongylus and combinations thereof.

In one embodiment of the endoparasites treated the endoparasite isHaemonchus contortus (H. contortus).

Yet another aspect of the invention is also directed toward a method oftreating an animal (e.g. a mammal or bird), against ectoparasiticinfection (e.g. insects) by administering an ectoparasiticidallyeffective amount of the composition of the invention. Mammals which canbe treated include but are not limited to humans, cats, dogs, cattle,chickens, cows, deer, goats, horses, llamas, pigs, sheep and yaks. Inone embodiment of the invention, the mammals treated are humans, cats ordogs.

In another embodiment for treatment against ectoparasites, theectoparasite is one or more insect or arachnid including those of thegenera Ctenocephalides, Rhipicephalus, Dermacentor, Ixodes, Boophilus,Ambylomma, Haemaphysalis, Hyalomma, Sarcoptes, Psoroptes, Otodectes,Chorioptes, Hypoderma, Damalinia, Linognathus, Haematopinus, Solenoptes,Trichodectes, and Felicola.

In another embodiment for the treatment against ectoparasites, theectoparasite is from the genera Ctenocephalides, Rhipicephalus,Dermacentor, Ixodes and/or Boophilus. The ectoparasites treated includebut are not limited to fleas, ticks, mites, mosquitoes, flies, lice,blowfly and combinations thereof. Specific examples include but are notlimited to cat and dog fleas (Ctenocephalides fells, Ctenocephalides sp.and the like), ticks (Rhipicephalus sp., Ixodes sp., Dermacentor sp.,Amblyoma sp. and the like), and mites (Demodex sp., Sarcoptes sp.,Otodectes sp. and the like), lice (Trichodectes sp., Cheyletiella sp.,Lignonathus sp., and the like), mosquitoes (Aedes sp., Culex sp.,Anopheles sp., and the like) and flies (Hematobia sp., Musca sp.,Stomoxys sp., Dematobia sp., Cochliomyia sp., and the like). In yetanother embodiment for the treatment against ectoparasites, theectoparasite is a flea and/or tick. Additional examples of ectoparasitesinclude but are not limited to the tick genus Boophilus, especiallythose of the species microplus (cattle tick), decoloratus and annulatus;myiases such as Dermatobia hominis (known as Berne in Brazil) andCochliomyia hominivorax (greenbottle); sheep myiases such as Luciliasericata, Lucilia cuprina (known as blowfly strike in Australia, NewZealand and South Africa). Flies proper, namely those whose adultconstitutes the parasite, such as Haematobia irritans (horn fly); licesuch as Linognathus vitulorum, etc.; and mites such as Sarcoptes scabiciand Psoroptes ovis. The above list is not exhaustive and otherectoparasites are well known in the art to be harmful to animals andhumans. These include, for example migrating dipterous larvae.

In another embodiment of the invention, the compounds and compositionsof the invention are suitable for controlling pests such as insectsselected from the group consisting of Blatella germanica, Heliothisvirescens, Leptinotarsa decemlineata, Tetramorium caespitum andcombinations thereof.

The phytoparasitic nematodes include, for example, Anguina spp.,Aphelenchoides spp., Belonoaimus spp., Bursaphelenchus spp., Ditylenchusdipsaci, Globodera spp., Heliocotylenchus spp., Heterodera spp.,Longidorus spp., Meloidogyne spp., Pratylenchus spp., Radopholussimilis, Rotylenchus spp., Trichodorus spp., Tylenchorhynchus spp.,Tylenchulus spp., Tylenchulus semipenetrans, Xiphinema spp.

In addition, with or without the other pesticidal agents added to thecomposition, the invention can also be used to treat other pests whichinclude but are not limited to pests:

-   (1) from the class of Isopoda, for example Oniscus asellus,    Armadillidium vulgare and Porcellio scaber;-   (2) from the class of Diplopoda, for example Blaniulus guttulatus;-   (3) from the class of Chilopoda, for example Geophilus carpophagus    and Scutigera spp.;-   (4) from the class of Symphyla, for example Scutigerella immaculata;-   (5) from the class of Thysanura, for example Lepisma saccharina;-   (6) from the class of Collembola, for example Onychiurus armatus;-   (7) from the class of Blattaria, for example Blatta orientalis,    Periplaneta americana, Leucophaea maderae and Blattella germanica;-   (8) from the class of Phthiraptera, for example Pediculus humanus    corporis, Haematopinus spp., Linognathus spp., Trichodectes spp. and    Damalinia spp.;-   (9) from the class of Hymenoptera, for example Diprion spp.,    Hoplocampa spp., Lasius spp., Monomorium pharaonis and Vespa spp.;-   (10) from the class of Siphonaptera, for example Xenopsylla cheopis    and Ceratophyllus spp.;-   (11) from the class of Anoplura (Phthiraptera), for example,    Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp.,    Trichodectes spp.;-   (12) from the class of Arachnida, for example, Acarus siro, Aceria    sheldoni, Aculops spp., Aculus spp., Amblyomma spp., Argas spp.,    Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Chorioptes    spp., Dermanyssus gallinae, Eotetranychus spp., Epitrimerus pyri,    Eutetranychus spp., Eriophyes spp., Hemitarsonemus spp., Hyalomma    spp., Ixodes spp., Latrodectus mactans, Metatetranychus spp.,    Oligonychus spp., Ornithodoros spp., Panonychus spp., Phyllocoptruta    oleivora, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus    spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus,    Stenotarsonemus spp., Tarsonemus spp., Tetranychus spp., Vasates    lycopersici.;-   (13) from the class of Bivalva, for example, Dreissena spp.;-   (14) from the class of Coleoptera, for example, Acanthoscelides    obtectus, Adoretus spp., Agelastica alni, Agriotes spp., Amphimallon    solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp.,    Anthrenus spp., Apogonia spp., Atomaria spp., Attagenus spp.,    Bruchidius obtectus, Bruchus spp., Ceuthorhynchus spp., Cleonus    mendicus, Conoderus spp., Cosmopolites spp., Costelytra zealandica,    Curculio spp., Cryptorhynchus lapathi, Dermestes spp., Diabrotica    spp., Epilachna spp., Faustinus cubae, Gibbium psylloides,    Heteronychus arator, Hylamorpha elegans, Hylotrupes bajulus, Hypera    postica, Hypothenemus spp., Lachnosterna consanguinea, Leptinotarsa    decemlineata, Lissorhoptrus oryzophilus, Lixus spp., Lyctus spp.,    Meligethes aeneus, Melolontha melolontha, Migdolus spp., Monochamus    spp., Naupactus xanthographus, Niptus hololeucus, Oryctes    rhinoceros, Oryzaephilus surinamensis, Otiorrhynchus sulcatus,    Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Popillia    japonica, Premnottypes spp., Psylliodes chrysocephala, Ptinus spp.,    Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp.,    Sphenophorus spp., Sternechus spp., Symphyletes spp., Tenebrio    molitor, Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus    spp., Zabrus spp.;-   (15) from the class of Diptera, for example, Aedes spp., Anopheles    spp., Bibio hortulanus, Calliphora erythrocephala, Ceratitis    capitata, Chrysomyia spp., Cochliomyia spp., Cordylobia    anthropophaga, Culex spp., Cuterebra spp., Dacus oleae, Dermatobia    hominis, Drosophila spp., Fannia spp., Gastrophilus spp., Hylemyia    spp., Hyppobosca spp., Hypoderma spp., Liriomyza spp., Lucilia spp.,    Musca spp., Nezara spp., Oestrus spp., Oscinella frit, Pegomyia    hyoscyami, Phorbia spp., Stomoxys spp., Tabanus spp., Tannia spp.,    Tipula paludosa, Wohlfahrtia spp.;-   (16) from the class of Gastropoda, for example, Arion spp.,    Biomphalaria spp., Bulinus spp., Deroceras spp., Galba spp., Lymnaea    spp., Oncomelania spp., Succinea spp.;-   (17) from the class of helminths, for example, Ancylostoma    duodenale, Ancylostoma ceylanicum, Acylostoma braziliensis,    Ancylostoma spp., Ascaris lubricoides, Ascaris spp., Brugia malayi,    Brugia timori, Bunostomum spp., Chabertia spp., Clonorchis spp.,    Cooperia spp., Dicrocoelium spp, Dictyocaulus filaria,    Diphyllobothrium latum, Dracunculus medinensis, Echinococcus    granulosus, Echinococcus multilocularis, Enterobius vermicularis,    Faciola spp., Haemonchus spp., Heterakis spp., Hymenolepis nana,    Hyostrongulus spp., Loa Loa, Nematodirus spp., Oesophagostomum spp.,    Opisthorchis spp., Onchocerca volvulus, Ostertagia spp., Paragonimus    spp., Schistosomen spp., Strongyloides fuellebomi, Strongyloides    stercoralis, Stronyloides spp., Taenia saginata, Taenia solium,    Trichinella spiralis, Trichinella nativa, Trichinella britovi,    Trichinella nelsoni, Trichinella pseudopsiralis, Trichostrongulus    spp., Trichuris trichuria, Wuchereria bancrofti.;-   (18) from the class of Heteroptera, for example, Anasa tristis,    Antestiopsis spp., Blissus spp., Calocoris spp., Campylomma livida,    Cavelerius spp., Cimex spp., Creontiades dilutus, Dasynus piperis,    Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus    spp., Eurygaster spp., Heliopeltis spp., Horcias nobilellus,    Leptocorisa spp., Leptoglossus phyllopus, Lygus spp., Macropes    excavatus, Miridae, Nezara spp., Oebalus spp., Pentomidae, Piesma    quadrats, Piezodorus spp., Psallus seriatus, Pseudacysta persea,    Rhodnius spp., Sahlbergella singularis, Scotinophora spp.,    Stephanitis nashi, Tibraca spp., Triatoma spp.;-   (19) from the class of Homoptera, for example, Acyrthosipon spp.,    Aeneolamia spp., Agonoscena spp., Aleurodes spp., Aleurolobus    barodensis, Aleurothrixus spp., Amrasca spp., Anuraphis cardui,    Aonidiella spp., Aphanostigma piri, Aphis spp., Arboridia apicalis,    Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacorthum solani,    Bemisia spp., Brachycaudus helichrysfi, Brachycolus spp.,    Brevicoryne brassicae, Calligypona marginata, Carneocephala fulgida,    Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon    fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chromaphis    juglandicola, Chrysomphalus ficus, Cecadulina mbila, Coccomytilus    halli, Coccus spp., crtyptomyzus ribis, Dalbulus spp., Dialeurodes    spp., Diaphorina spp., Diaspis spp., Doralis spp., Drosicha spp.,    Dysaphis spp., Dysmicoccus spp., Empoasca spp., Eriosoma spp.,    Erythroneura spp., Euscelis bilobatus, Geococcus coffeae,    Homalodisca coagulata, Hyalopterus arundinis, Icerya spp., Idiocerus    spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp.,    Lepidosaphes spp., Lipaphis erysimi, Macrosiphum spp., Mahanarva    fimbriolata, Melanaphis sacchari, Metcalfiella spp., Metopolophium    dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp.,    Nasonovia ribisnigri, Nephotettix spp., Nilaparvata lugens,    Oncometopia spp., Orthezia praelonga, Parabemisia myricae,    Paratrioza spp., Parlatoria spp., Pemphigus spp., Peregrinus maidis,    Phenacoccus spp., Phloeomyzus passerinii, Phorodon humuli,    Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp.,    Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus    spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus    spp., Quesada gigas, Rastrococcus spp., Rhopalosiphum spp.,    Saissetia spp., Scaphoides titanus, Schizaphis graminum,    Selenaspidus articulatus, Sogata spp., Sogatella furcifera,    Sogatodes spp., Stictocephala festina, Tenalaphara malayensis,    Tinocallis caryaefoliae, Tomaspis spp., Toxoptera spp., Trialeurodes    vaporariorum, Trioza spp., Typhlocyba spp., Unaspis spp., Viteus    vitifolii.;-   (20) from the class of Isoptera, for example, Reticulitermes spp.,    Odontotermes spp.;-   (21) from the class of Lepidoptera, for example, Acronicta major,    Aedia leucomelas, Agrotis spp., Alabama argillacea, Anticarsia spp.,    Barathra brassicae, Bucculatrix thurberiella, Bupalus piniarius,    Cacoecia podana, Capua reticulana, Carpocapsa pomonella, Chematobia    brumata, Chilo spp., Choristoneura fumiferana, Clysia ambiguella,    Cnaphalocerus spp., Earias insulana, Ephestia kuehniella, Euproctis    chrysorrhoea, Euxoa spp., Feltia spp., Galleria mellonella,    Helicoverpa spp., Heliothis spp., Hofmannophila pseudospretella,    Homona magnanima, Hyponomeuta padella, Laphygma spp., Lithocolletis    blancardella, Lithophane antennata, Loxagrotis albicosta, Lymantria    spp., Malacosoma neustria, Mamestra brassicae, Mocis repanda,    Mythimna separata, Oria spp., Oulema oryzae, Panolis flammea,    Pectinophora gossypiella, Phyllocnistis citrella, Pieris spp.,    Plutella xylostella, Prodenia spp., Pseudaletia spp., Pseudoplusia    includens, Pyrausta nubilalis, Spodoptera spp., Thermesia    gemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix    viridana, Trichoplusia spp.;-   (22) from the class of Orthoptera, for example, Acheta domesticus,    Blatta orientalis, Blattella germanica, Gryllotalpa spp., Leucophaea    maderae, Locusta spp., Melanoplus spp., Periplaneta americana,    Schistocerca gregaria.;-   (23) from the class of Thysanoptera, for example, Baliothrips    biformis, Enneothrips flavens, Frankliniella spp., Heliothrips spp.,    Hercinothrips femoralis, Kakothrips spp., Rhipiphorothrips    cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp.;-   (24) from the class of Protozoa, for example, Eimeria spp.

In each aspect of the invention, the compounds and compositions of theinvention can be applied against a single pest or combinations thereof.

If appropriate, the compounds according to the invention can, at certainconcentrations or application rates, also be used as herbicides,safeners, growth regulators or agents to improve plant properties, or asmicrobicides, for example as fungicides, antimycotics, bactericides,viricides (including agents against viroids) or as agents against MLO(mycoplasma-like organisms) and RLO (rickettsia-like organisms). Ifappropriate, they can also be employed as intermediates or precursorsfor the synthesis of other active compounds.

The active compounds according to the invention, in combination withgood plant tolerance and favourable toxicity to warm-blooded animals andbeing tolerated well by the environment, are suitable for protectingplants and plant organs, for increasing the harvest yields, forimproving the quality of the harvested material and for controllinganimal pests, in particular insects, arachnids, helminths, nematodes andmolluscs, which are encountered in agriculture, in horticulture, inanimal husbandry, in forests, in gardens and leisure facilities, in theprotection of stored products and of materials, and in the hygienesector. They may be preferably employed as plant protection agents. Theyare active against normally sensitive and resistant species and againstall or some stages of development.

The invention is further described by the following non-limitingexamples which further illustrate the invention, and are not intended,nor should they be interpreted to, limit the scope of the invention.

EXAMPLES

All temperatures are given in degrees Centigrade; room temperature means20 to 25° C. Reagents were purchased from commercial sources or preparedfollowing literature procedures. Proton and fluorine magnetic resonance(respectively 1H NMR and 19F NMR) spectra were recorded on a VarianINOVA NMR spectrometer [400 MHz (1H) or 500 MHz (1H) and 377 MHz (19F)].All spectra were determined in the solvents indicated. Chemical shiftsare reported in ppm downfield of tetramethylsilane (TMS), referenced tothe residual proton peak of the respective solvent peak for 1H NMR.Interproton coupling constants are reported in Hertz (Hz).

LC-MS spectra were either obtained using a Thermofinnigan AQA MS ESIinstrument, using a Phenomenex Aqua 5 micron C18 125A 50×4.60 mm columnand a linear gradient from 55% methanol: 1% acetonitrile in water to100% methanol over 3 minutes. 100% methanol was maintained for 2minutes. Alternatively, LCMS spectra were obtained using an Agilent1200SL HPLC equipped with a 6130 mass spectrometer operating withelectrospray ionization; chromatographic data were obtained using aShimadzu Shim-pack XR-ODS, 3.0×30 mm, 2.2 micron particle size columnand a water:methanol gradient from 15% methanol to 95% methanol in 2.2minutes under a 1.5 mL/min flow; a hold at 95% methanol was applied atthe end of the gradient for 0.8 minutes; and both water and methanolmobile phases contained 0.1% formic acid.

Example 1N-[1-Methyl-1-thiocarbamoyl-2-(4,5,7-trichloro-2H-benzotriazol-2-yl)-ethyl]-4-trifluoromethoxybenzamide(compound No 1)

A solution ofN-[1-Cyano-1-methyl-2-(4,5,7-trichloro-2H-benzotriazol-2-yl)-ethyl]-4-trifluoromethoxybenzamide(60 mg, 0.12 mmole, described in U.S. Provisional Application SN:60/930,485 as compound 1.064) and ammonium sulfide (0.04 mL, 40-48 wt. %in water from Sigma-Aldrich) in methanol (4 mL) was irradiated for 20minute in a self-tunable CEM microwave Discover synthesizer at 80° C.(initial power 100 Watts) and then cooled using a flow of compressedair, evaporated in vacuo and partitioned between ethyl acetate andwater. The aqueous layer was further extracted with ethyl acetate. Theorganic extracts were combined, washed with brine, washed with brine,dried over anhydrous magnesium sulfate, filtered and concentrated underreduced pressure to give a residue that that was purified bychromatography (SiO₂, heptane/ethyl acetate) to afford the titlecompound as a solid (30 mg, 47%) along with recovered starting material(22 mg, 37%). MS (ES): M/Z [M+H]=526 and [M−H]=524. 1H NMR: (400 MHz,DMSO-d₆): 1.48 (s, 3H), 5.59 (d, J=13.3 Hz, 1H), 5.70 (, J=13.3 Hz, 1H),7.44 (d, J=8.0 Hz, 2H), 7.88 (s, 1H), 7.93 (d, J=8.8 Hz, 2H), 8.16 (s,1H), 9.34 (s, 1H) and 9.83 (s, 1H). 19F NMR (376 MHz, DMSO-d₆): −57.2(s, 3F).

Example 2N-[1-Methyl-1-thiocarbamoyl-2-(4,5,7-trichloro-2H-benzotriazol-2-yl)-ethyl]-4-trifluoromethylthiobenzamide(compound No 2)

Using a procedure similar to that described in Example 1, except usingN-[1-Cyano-1-methyl-2-(4,5,7-trichloro-2H-benzotriazol-2-yl)-ethyl]-4-trifluoromethylthiobenzamide(70 mg, 0.14 mmole, described in U.S. Provisional Application SN:60/930,485 as compound No 1.065), the title compound was isolated as asolid (37 mg, 49%). MS (ES): M/Z [M+H]=542 and [M−H]=540. 1H NMR: (400MHz, DMSO-d₆): 1.48 (s, 3H), 5.56-5.64 (m, 1H), 5.66-5.76 (m, 1H), 7.80(d, J=8.3 Hz, 2H), 7.88 (s, 1H), 7.93 (d, J=8.4 Hz, 2H), 8.25 (s, 1H),9.36 (s, 1H) and 9.84 (s, 1H). 19F NMR (376 MHz, DMSO-d₆): −42.2 (s,3F).

Example 3N-[2-(4-Cyano-2-trifluoromethylphenoxy)-1-methyl-1-thiocarbamoyl-ethyl]-4-trifluoromethoxybenzamide(compound No 3)

Using a procedure similar to that described in Example 1, except usingN-[1-Cyano-2-(4-cyano-2-trifluoromethylphenoxy)-1-methyl-ethyl]-4-trifluoromethoxybenzamide(588 mg, 1.28 mmole, described in WO 2005/044784 as compound 2.6), thetitle compound was isolated as a solid (180 mg, 28%). MS (ES): M/Z[M+H]=492 and [M−H]=490. 1H NMR: (400 MHz, DMSO-d₆): 1.67 (s, 3H), 4.82(d, J=9.4 Hz, 1H), 4.98 (d, J=9.4 Hz, 1H), 7.38 (d, J=8.5 Hz, 1H), 7.45(d, J=8.0 Hz, 2H), 7.90-8.01 (m, 2H), 8.07 (d, J=2.1 Hz, 2H), 8.68 (s,1H), 9.19 (s, 1H) and 9.82 (s, 1H). 19F NMR (376 MHz, DMSO-d₆): −61.9(s, 3F) and −57.1 (s, 3F).

Example 4N-[1-Methyl-1-thiocarbamoyl-2-(4-thiocarbamoyl-2-trifluoromethylphenoxy)-ethyl]-4-trifluoromethoxybenzamide(compound No 4)

From the same reaction mixture described in Example 3 above was alsoisolated the corresponding bis-thioamide title compound No 4 (380 mg,56%). MS (ES): M/Z [M+H]=526 and [M−H]=524. 1H NMR: (400 MHz, DMSO-d₆):1.68 (s, 3H), 4.77 (d, J=9.4 Hz, 1H), 4.94 (d, J=9.4 Hz, 1H), 7.23 (d,J=9.6 Hz, 1H), 7.45 (d, J=8.1 Hz, 2H), 7.91-8.05 (m, 2H), 8.20 (d, J=2.3Hz, 2H), 8.66 (s, 1H), 9.18 (s, 1H), 9.54 (s, 1H), 9.81 (s, 1H) and 9.85(br. s., 1H). 19F NMR (376 MHz, DMSO-d₆): −61.4 (s, 3F) and −57.1 (s,3F).

Example 5N-[2-(5-Cyano-2-trifluoromethylphenoxy)-1-methyl-1-thiocarbamoyl-ethyl]-4-trifluoromethylthiobenzamide(compound No 5)

Using a procedure similar to that described in Example 1, except usingN-[1-Cyano-2-(5-cyano-2-trifluoromethylphenoxy)-1-methyl-ethyl]-4-trifluoromethylthiobenzamide(672 mg, 1.42 mmole, described in WO 2005/044784 as compound 3.16), thetitle compound was isolated as a solid (124 mg, 17%). MS (ES): M/Z[M+H]=508 and [M−H]=506. 1H NMR: (400 MHz, DMSO-d₆): 1.68 (s, 3H), 4.78(d, J=9.5 Hz, 1H), 4.93 (d, J=9.4 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.74(s, 1H), 7.77 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.95 (d, J=8.4Hz, 2H), 8.75 (s, 1H), 9.17 (s, 1H) and 9.83 (s, 1H). 19F NMR (376 MHz,DMSO-d₆): −62.1 (s, 3F) and −42.1 (s, 3F).

Example 64-Hydroxy-N-[1-methyl-2-(2-methyl-5-thiocarbamoyl-phenoxy)-1-thiocarbamoyl-ethyl]-4-trifluoromethylthiobenzamide(compound No 6)

From the same reaction mixture described in Example 5 above was alsoisolated the corresponding bis-thioamide title compound No 6 (152 mg,20%). MS (ES): M/Z [M+H]=542 and [M−H]=540. 1H NMR: (400 MHz, DMSO-d₆):1.69 (s, 3H), 4.75 (d, J=9.2 Hz, 1H), 4.93 (d, J=9.1 Hz, 1H), 7.50 (d,J=8.1 Hz, 1H), 7.56 (s, 1H), 7.61 (d, J=8.2 Hz, 1H), 7.80 (d, J=8.1 Hz,2H), 7.97 (d, J=8.2 Hz, 2H), 8.73 (s, 1H), 9.20 (br. s., 1H), 9.76 (br.s., 1H), 9.82 (br. s., 1H) and 10.11 (br. s., 1H). 19F NMR (376 MHz,DMSO-d₆): −61.4 (s, 3F) and −42.1 (s, 3F).

Example 7N-[2-(5-Cyano-2-trifluoromethylphenoxy)-1-methyl-1-thiocarbamoyl-ethyl]-4-trifluoromethoxybenzamide(compound No 7)

Using a procedure similar to that described in Example 1, except usingN-[1-Cyano-2-(5-cyano-2-trifluoromethylphenoxy)-1-methyl-ethyl]-4-trifluoromethoxybenzamide(230 mg, 0.5 mmole, described in WO 2005/044784 as compound 2.6), thetitle compound was isolated as a solid (39 mg, 16%). MS (ES): M/Z[M+H]=492 and [M−H]=490. 1H NMR: (400 MHz, DMSO-d₆): 1.68 (s, 3H), 4.79(d, J=9.5 Hz, 1H), 4.92 (d, J=9.5 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.55(d, J=8.2 Hz, 1H), 7.77 (d, J=8.1 Hz, 2H), 7.88-8.08 (m, 2H), 8.67 (s,1H), 9.15 (s, 1H) and 9.83 (s, 1H). 19F NMR (376 MHz, DMSO-d₆): −62.1(s, 3F) and −57.1 (s, 3F).

Example 84-Hydroxy-N-[1-methyl-2-(2-methyl-5-thiocarbamoyl-phenoxy)-1-thiocarbamoyl-ethyl]-4-trifluoromethoxybenzamide(compound No 8)

From the same reaction mixture described in Example 7 above was alsoisolated the corresponding bis-thioamide title compound No 8 (21 mg,8%). MS (ES): M/Z [M+H]=526 and [M−H]=524. 1H NMR: (400 MHz, DMSO-d₆):1.68 (s, 3H), 4.75 (d, J=9.3 Hz, 1H), 4.92 (d, J=9.2 Hz, 1H), 7.45 (d,J=8.0 Hz, 2H), 7.51 (s, 1H), 7.56 (s, 1H), 7.61 (d, J=8.2 Hz, 1H),7.94-8.05 (m, 2H), 8.66 (s, 1H), 9.18 (s, 1H), 9.76 (br. s., 1H), 9.81(s, 1H) and 10.11 (br. s., 1H). 19F NMR (376 MHz, DMSO-d₆): −61.4 (s,3F) and −57.1 (s, 3F).

Method of Use Examples

Method A: Screening Method to Test Activity of Compounds AgainstHaemonchus contortus.

Twenty L1 Haemonchus contortus larvae were added to wells of amicrotitre plate containing a nutrient medium and the test compound inDMSO. The microtitre plate was then held at 27° C. where the L1 larvaewere allowed to develop. An analysis was conducted at 4 days todetermine successful development to the L3 stage. Larvae exposed to DMSOand no test compound served as controls. Compounds numbers 3, 4, 6 and 8gave at least 90% motility inhibition at a test concentration of 0.15ppm at the 4 days assessment. Compounds numbers 1, 2, 5 and 7 gave atleast 90% motility inhibition at a test concentration of 0.01 ppm at the4 days assessment.

Method B: Screening Method to Test Activity of Compounds AgainstHaemonchus contortus in Vivo on Mongolian Jirds (Meriones unguiculatus).

Mongolian jirds, at least five weeks old, were immunosuppressed andartificially infected with ca. 1000 ensheathed Haemonchus contortusthird instar larvae. Six days after infection, the jirds were treated byoral gavage with the test compounds, dissolved in a mixture of 2 partsDMSO and 1 part polyethylene glycol (PEG400), at doses of 100 mg/kg and10 mg/kg. Jirds treated only with the placebo (2 parts DMSO and 1 partPEG400) served as controls. On day 9 (3 days after treatment) the jirdswere euthanized and necropsied for recovery of parasites from thestomach. Efficacy was calculated as the average % reduction in thenumber of worms in each test group compared with the average number ofworms from the control group. In this screen, a vast reduction innematode infestation was achieved with compounds of formula (I) and(Ia). Compound number 1, provided at least 95% reduction in nematodeinfestation at a dose as low as 1 or 10 mg/kg.

Having thus described in detail various embodiments of the presentinvention, it is to be understood that the invention defined by theabove paragraphs is not to be limited to particular details set forth inthe above description as many apparent variations thereof are possiblewithout departing from the spirit or scope of the present invention.

1. A thioamide compound of formula (I):

wherein R₁, R₂, R₈, R₉, R₁₀ and R₁₁, independently of one another, arehydrogen, cyano, nitro, halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl,halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo C₁-C₆-alkylthio,C₁-C₆-alkylsulfinyl, halo C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, haloC₁-C₆-alkylsulfonyl, SF₅, arylthio, C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino, unsubstituted or substitutedaryl, or unsubstituted or substituted phenoxy, whereby the substituentsmay each be independent of one another and are selected from the groupconsisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,halo-C₁-C₆-alkylsulfonyl, SF₅, and methylthioamino; R₃, R₄ and R₅,independently of one another, are hydrogen, halogen, C₁-C₆-alkyl,halo-C₁-C₆-alkyl; C₃-C₇-cycloalkyl that is either unsubstituted orsubstituted, whereby the substituents may each be independent of oneanother and are selected from the group consisting of halogen andC₁-C₆-alkyl; and phenyl that is either unsubstituted or substituted,whereby the substituents may each be independent of one another and areselected from the group consisting of cyano, nitro, halogen,C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio,arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl,C₁-C₆-alkylsulfonyl, halo-C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino,and di(C₁-C₆-alkyl)amino; or R₄ and R₅ together signify C₂-C₆-alkylene;R₆ is hydrogen, C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,C₁-C₆-alkylcarbonyl, C₁-C₆-alkylthiocarbonyl or benzyl that is eitherunsubstituted or substituted, whereby the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo-C₁-C₆-alkylsulfonyl,SF₅, C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; R₇ is hydrogen,C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkylcarbonyl,C₁-C₆-alkylthiocarbonyl, phenyl that is either unsubstituted orsubstituted, whereby the substituents may each be independent of oneanother and are selected from the group consisting of cyano, nitro,halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino,and di(C₁-C₆-alkyl)amino; heteroaryl that is either unsubstituted orsubstituted, whereby the substituents may each be independent of oneanother and are selected from the group consisting of cyano, nitro,halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino,and di(C₁-C₆-alkyl)amino; or naphtyl or quinlyl that is eitherunsubstituted or substituted, whereby the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino, anddi(C₁-C₆-alkyl)amino; P is C—R₁ or N; Q is C—R₂ or N; V is C—R₈ or N; Wis C—R₉ or N; X is C—R₁₀ or N; Y is C—R₁₁ or N; Z is a direct bond,C(O), C(S) or S(O)_(p); a is 1, 2 or 3; and P is 1 or
 2. 2. The compoundof claim 1, wherein: P and Q is N; V is C—R₈; W is C—R₉; X is C—R₁₀; Yis C—R₁₁; R₈, R₉, R₁₀ and R₁₁, independently of one another, are cyano,nitro, halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl, halo-C₁-C₆-alkyl,C₁-C₆-alkylthio, halo C₁-C₆-alkylthio, C₁-C₆-alkylsulfinyl, haloC₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo C₁-C₆-alkylsulfonyl, SF₅,arylthio, C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, unsubstituted or substituted aryl or unsubstitutedor substituted phenoxy, whereby the substituents may each be independentof one another and are selected from the group consisting of cyano,nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo-C₁-C₆-alkylsulfonyl,SF₅, and methylthioamino; R₃, R₄ and R₆ are H; R₅ is methyl orC₁-C₃-alkyl; R₇ is unsubstituted or substituted phenyl wherein thesubstituents may each be independent of one another and are selectedfrom the group consisting of cyano, nitro, halogen, C₁-C₆-alkyl,halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio,C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl,C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino;unsubstituted or substituted heteroaryl, wherein the substituents mayeach be independent of one another and are selected from the groupconsisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅,C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; or unsubstituted orsubstituted naphthyl or quinolyl, wherein the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino, anddi(C₁-C₆-alkyl)amino; Z is a direct bond, C(O), C(S) or S(O)_(p); and ais
 1. 3. The compound of claim 1, wherein: P and Q is N; V is C—R₈; W isC—R₉; X is C—R₁₀; Y is C—R₁₁; R₈, R₉, R₁₀ and R₁₁, independently of oneanother, is cyano, nitro, halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl,halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo C₁-C₆-alkylthio,C₁-C₆-alkylsulfinyl, halo C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, haloC₁-C₆-alkylsulfonyl, SF₅, arylthio, C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino, unsubstituted or substitutedaryl or unsubstituted or substituted phenoxy, whereby the substituentsmay each be independent of one another and are selected from the groupconsisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl,halo-C₁-C₆-alkylsulfonyl, SF₅, and methylthioamino; R₃, R₄ and R₆ is H;R₅ is methyl or C₁-C₃-alkyl; R₇ is unsubstituted or substituted phenylwherein the substituents may each be independent of one another and areselected from the group consisting of cyano, nitro, halogen,C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio,arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl,C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino;unsubstituted or substituted heteroaryl, wherein the substituents mayeach be independent of one another and are selected from the groupconsisting of cyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl,C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy,halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl,C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅,C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; Z is C(O); a is
 1. 4. Thecompound of claim 1, wherein: P and Q is N; V is C—R₈; W is C—R₉; X isC—R₁₀; Y is C—R₁₁; R₈, R₉, R₁₀ and R₁₁, independently of one another, iscyano, nitro, halogen, C₁-C₆-alkyl, C₃-C₇-cycloalkyl, halo-C₁-C₆-alkyl,C₁-C₆-alkylthio, halo C₁-C₆-alkylthio, C₁-C₆-alkylsulfinyl, haloC₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo C₁-C₆-alkylsulfonyl, SF₅,arylthio, C₁-C₆-alkoxy, C₃-C₇-cycloalkyloxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, unsubstituted or substituted aryl or unsubstitutedor substituted phenoxy, whereby the substituents may each be independentof one another and are selected from the group consisting of cyano,nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, halo-C₁-C₆-alkylsulfonyl,SF₅, and methylthioamino; R₃, R₄ and R₆ is H; R₅ is methyl; R₇ isunsubstituted or substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl,halo-C₁-C₆-alkylsulfinyl, C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino,and di(C₁-C₆-alkyl)amino; unsubstituted or substituted heteroaryl,wherein the substituents may each be independent of one another and areselected from the group consisting of cyano, nitro, halogen,C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio,arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,halo-C₁-C₆-alkylcarbonyl, C₁-C₆-alkylsulfinyl, halo-C₁-C₆-alkylsulfinyl,C₁-C₆-alkylsulfonyl, SF₅, C₁-C₆-alkylamino, and di(C₁-C₆-alkyl)amino; Zis C(O) a is 1; m and n are independently 0 or
 1. 5. The compound ofclaim 1, wherein: R₁, R₂, R₈, R₉, R₁₀ and R₁₁, independently of oneanother, is hydrogen, cyano, halogen, halomethyl or methylthioamino; R₃,R₄ and R₆ is H; R₅ is methyl or C₁-C₃-alkyl; P is C—R₁ or N; Q is C—R₂or N; V is C—R₈ or N; W is C—R₉; X is C—R₁₀; Y is C—R₁₁ or N; Z is C(O);and a is
 1. 6. The compound of claim 1, wherein: R₁, R₂, R₈, R₉, R₁₀ andR₁₁, independently of one another, is hydrogen, cyano, chloro ortrifluoromethyl; R₃, R₄ and R₆ is H; R₅ is methyl; P is C—R₁ or N; Q isC—R₂ or N; V is C—R₈ or N; W is C—R₉; X is C—R₁₀; Y is C—R₁₁ or N; Z isC(O); R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofcyano, nitro, halogen, C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio,halo-C₁-C₆-alkylthio, arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy,C₁-C₆-alkylcarbonyl, halo-C₁-C₆-alkylcarbonyl, and a is
 1. 7. Thecompound of claim 1, wherein: R₈, R₉, R₁₀ and R₁₁, independently of oneanother, is hydrogen, cyano, chloro or trifluoromethyl; R₃, R₄ and R₆ isH; R₅ is methyl; P is N; Q is N; V is C—R₈; W is C—R₉; X is C—R₁₀; Y isC—R₁₁; Z is C(O); R₇ is a substituted phenyl wherein the substituentsmay each be independent of one another and are selected from the groupconsisting of halogen, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio,C₁-C₆-alkoxy, and halo-C₁-C₆-alkoxy, and a is
 1. 8. The compound ofclaim 1, wherein: R₈, R₉, R₁₀ and R₁₁, independently of one another, ishydrogen, cyano, chloro or trifluoromethyl; R₃, R₄ and R₆ is H; R₅ ismethyl; P is N; Q is N; V is C—R₈; W is C—R₉; X is C—R₁₀; Y is C—R₁₁; Zis C(O); R₇ is a substituted phenyl wherein the substituents may each beindependent of one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and a is
 1. 9. The compoundof claim 1, wherein: R₁, R₈, R₉, R₁₀ and R₁₁, independently of oneanother, is hydrogen, cyano, chloro, triifluoromethyl or methylamino;R₃, R₄ and R₆ is H; R₅ is methyl; P is C—R₁ or N; V is C—R₈ or N; W isC—R₉; X is C—R₁₀; Y is C—R₁₁ or N; Z is C(O); R₇ is a substituted phenylwherein the substituents may each be independent of one another and areselected from the group consisting of cyano, nitro, halogen,C₁-C₆-alkyl, halo-C₁-C₆-alkyl, C₁-C₆-alkylthio, halo-C₁-C₆-alkylthio,arylthio, C₁-C₆-alkoxy, halo-C₁-C₆-alkoxy, C₁-C₆-alkylcarbonyl,halo-C₁-C₆-alkylcarbonyl, and a is
 1. 10. The compound of claim 1,wherein: R₉, R₁₀ and R₁₁, independently of one another, are hydrogen,cyano, chloro, bromo, methyl or trifluoromethyl; R₃, R₄ and R₆ are H; R₂is H, chloro, bromo or C₁-C₆-alkoxy; R₅ is methyl; P is N; Q is C—R₂; Vis N; W is C—R₉; X is C—R₁₀; Y is C—R₁₁; Z is C(O); R₇ is a substitutedphenyl wherein the substituents may each be independent of one anotherand are selected from the group consisting of halo-C₁-C₆-alkylthio andhalo-C₁-C₆-alkoxy, and a is
 1. 11. The compound of claim 1, wherein: R₈,R₉, R₁₀ and R₁₁, independently of one another, are hydrogen, chloro,bromo, methyl or trifluoromethyl; R₃, R₄ and R₆ is H; R₂ is H, chloro,bromo or C₁-C₆-alkoxy; R₅ is methyl; P is N; Q is C—R₂; V is C—R₈; W isC—R₉; X is C—R₁₀; Y is C—R₁₁; Z is C(O); R₇ is a substituted phenylwherein the substituents may each be independent of one another and areselected from the group consisting of halo-C₁-C₆-alkylthio andhalo-C₁-C₆-alkoxy, and a is
 1. 12. The compound of claim 1, wherein: R₉,R₁₀ and R₁₁, independently of one another, is hydrogen, cyano, chloro,bromo, methyl or trifluoromethyl; R₃, R₄ and R₆ is H; R₅ is methyl; P isN; Q is N; V is C—R₈; W is C—R₉; X is C—R₁₀; Y is C—R₁₁; Z is C(O); R₇is a substituted phenyl wherein the substituents may each be independentof one another and are selected from the group consisting ofhalo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy, and a is
 1. 13. The compoundof claim 1, wherein: R₉, R₁₀ and R₁₁, independently of one another, arehydrogen, chloro, bromo or methyl; R₃, R₄ and R₆ are H; R₂ is H, chloro,bromo or methoxy; R₅ is methyl; P is N; Q is C—R₂; V is N; W is C—R₉; Xis C—R₁₀; Y is C—R₁₁; Z is C(O); R₇ is a substituted phenyl wherein thesubstituents may each be independent of one another and are selectedfrom the group consisting of halo-C₁-C₆-alkylthio and halo-C₁-C₆-alkoxy,and a is
 1. 14. The compound of claim 1, wherein: R₈, R₉, R₁₀ and R₁₁,independently of one another, are hydrogen, chloro, bromo, methyl ortrifluoromethyl; R₃, R₄ and R₆ is H; R₂ is H, chloro, bromo, methoxy,ethoxy, propoxy or butoxy; R₅ is methyl; P is N; Q is C—R₂; V is C—R₈; Wis C—R₉; X is C—R₁₀; Y is C—R₁₁; Z is C(O); R₇ is a substituted phenylwherein the substituents may each be independent of one another and areselected from the group consisting of halo-C₁-C₆-alkylthio andhalo-C₁-C₆-alkoxy, and a is
 1. 15. A method of producing the compoundsof claim 1, wherein the compound of formula (I) are produced by aprocess which comprises: reacting a compound of formula (II)

with ammonium sulfide or sodium hydrosulfide wherein R₃, R₄, R₅, R₆, R₇,P, Q, V, W, X, Y, Z, a, are as defined above for the compounds offormula (I) in a solvent with or without the presence of base.
 16. Amethod of treating an animal against endoparasitic infection, whereinthe endoparasitic infection is a helminth, by administering anendoparasiticidally effective amount of the compound of claim 1 to ananimal in need thereof.
 17. The method of claim 16, wherein the helminthis Haemonchus contortus.